CB1 receptors on different cell types (glutamate neurons, GABA neurons, astrocytes, mitochondria) produce distinct and sometimes opposite effects on memory and feeding behavior.
Read this if you want to understand why cannabis affects so many different brain functions at once.
Same receptor, different cell types, different behavioral effects
What the researchers found
This review examined how the location of CB1 receptors across different brain cell types and subcellular compartments determines the specific behavioral effects of cannabinoids. CB1 receptors are widely distributed across the brain on glutamatergic neurons, GABAergic neurons, astrocytes, and even on mitochondria within cells.
The same receptor produces different molecular and cellular effects depending on which cell type expresses it. For example, CB1 receptors on glutamatergic neurons and GABAergic neurons mediate different aspects of memory and feeding. CB1 receptors on astrocytes contribute to memory through distinct mechanisms. Even CB1 receptors on mitochondria within cells influence energy metabolism differently.
The authors argued that understanding these site-specific actions is essential for developing targeted cannabinoid-based medicines that produce desired effects without unwanted ones.
Why it matters
The location-dependent effects of CB1 receptors explain why cannabis produces such a wide range of effects simultaneously. This knowledge could enable development of cannabinoid medicines that target specific cell types to treat conditions like appetite disorders or memory problems without broad side effects.
The numbers in context
CB1 receptors identified on at least 4 cell types (glutamatergic neurons, GABAergic neurons, astrocytes, mitochondria). Effects analyzed in two behavioral domains: memory and feeding.
How the study worked
Narrative review synthesizing research on cell-type-specific and subcellular-compartment-specific functions of CB1 receptors, with a focus on memory and feeding behavior.
What this study cannot tell us
Much of the evidence comes from genetic knockout mice, which completely remove receptors from cell types rather than modulating them. Human confirmation of cell-type-specific effects is limited.
How to read the evidence
Narrative review of predominantly preclinical research on cell-type-specific CB1 receptor functions.
When this study was published
Published in 2015. Cell-type-specific cannabinoid research has continued to advance.
The bigger picture
Cannabis affects so many different functions because its receptors are found on virtually every type of brain cell. The next generation of cannabinoid medicines may need to target specific cell populations rather than activating all CB1 receptors indiscriminately.
Questions still open
- Can drugs be designed to target CB1 receptors on specific cell types? How do the relative proportions of CB1 receptors on different cells change with chronic cannabis use?
Common questions
Why does cannabis affect both memory and appetite?
Could targeted cannabinoid drugs avoid side effects?
Read the original research
Dissecting the cannabinergic control of behavior: The where matters.
BioEssays : news and reviews in molecular, cellular and developmental biology, 37(11), 1215-25
Citation
Busquets-Garcia, Arnau; Desprez, Tifany; Metna-Laurent, Mathilde; Bellocchio, Luigi; Marsicano, Giovanni; Soria-Gomez, Edgar. (2015). Dissecting the cannabinergic control of behavior: The where matters.. BioEssays : news and reviews in molecular, cellular and developmental biology, 37(11), 1215-25. https://doi.org/10.1002/bies.201500046
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