Cannabidiol boosts social learning by enhancing brain acetylcholine signaling, study finds

New research published in Psychopharmacology shows that cannabidiol, a major non-psychoactive compound in cannabis, can enhance a specific type of social memory in mice. This effect appears to be linked to changes in acetylcholine signaling in a key brain region called the basal forebrain. The findings provide new insight into how cannabidiol might influence cognitive processes and social behavior.

Cannabidiol, commonly known as CBD, is often promoted for its therapeutic effects on anxiety and cognition. However, the precise brain mechanisms underlying these effects remain unclear. In this study, researchers from National Cheng Kung University in Taiwan explored whether CBD could enhance social learning in mice by modulating a brain chemical called acetylcholine, which plays an important role in memory and attention.

The focus of the study was on a behavior known as socially transmitted food preference. This type of learning allows mice to acquire information about safe food choices by interacting with other mice that have eaten specific flavored foods. This behavior depends on memory and social interaction and is used as a model for studying cognitive processes related to social learning.

The researchers conducted a series of experiments using male C57BL/6J mice, a common strain in laboratory research. They administered a single dose of CBD (20 mg/kg) to observer mice 30 minutes before a social interaction with a demonstrator mouse that had recently eaten a flavored food. After this interaction, the observer mice were tested to see whether they would preferentially consume the same flavored food, indicating that they had learned and remembered the social cue.

The researchers found that mice treated with CBD showed a significantly stronger preference for the food flavor eaten by the demonstrator compared to untreated mice. This enhancement was observed both immediately after the social interaction and 24 hours later, suggesting that CBD strengthened both short-term and longer-lasting memory for socially acquired information.

To understand how CBD might produce this effect, the researchers examined the role of acetylcholine, a neurotransmitter that is critical for learning and memory. Acetylcholine is produced in the basal forebrain and acts on receptors in various parts of the brain, including the hippocampus and prefrontal cortex.

In one experiment, the researchers reduced the activity of an enzyme called acetylcholinesterase, which breaks down acetylcholine in the brain. By injecting a substance known as an antisense oligodeoxynucleotide directly into the brain, they lowered acetylcholinesterase levels in the basal forebrain. This treatment also enhanced food preference memory in mice, mimicking the effects of CBD.

In another experiment, they gave mice a drug called scopolamine, which blocks muscarinic acetylcholine receptors. When mice were treated with both scopolamine and CBD, the memory-enhancing effect of CBD disappeared. This suggested that muscarinic receptors are essential for the cognitive benefits of CBD in this context.

To further probe the relationship between CBD and acetylcholine, the researchers measured acetylcholine levels in the basal forebrain after CBD administration. Interestingly, although there was no overall increase in acetylcholine levels across all CBD-treated mice, those that showed stronger food preference memory also had higher acetylcholine levels in this brain region. This correlation did not exist in the untreated mice.

These results suggest that CBD enhances social learning and memory by increasing acetylcholine signaling in mice that are responsive to the treatment. In particular, activation of muscarinic receptors in the basal forebrain appears to be necessary for this cognitive effect.

Importantly, the researchers ruled out several alternative explanations for their findings. CBD did not affect the mice’s overall food consumption, movement, or basic social behavior. Nor did it impair or enhance their ability to detect and discriminate between odors, a critical aspect of the socially transmitted food preference task. While CBD did reduce anxiety-like behavior shortly after administration, this effect had faded by the time of the 24-hour memory test, suggesting it did not account for the observed changes in memory.

The study highlights individual differences in how animals respond to CBD. Not all CBD-treated mice showed increased acetylcholine levels or improved memory. Only a subset appeared to benefit, which the researchers suggest may have implications for personalized medicine. In clinical contexts, CBD might enhance cognition in some individuals but have limited or no effects in others.

The findings also support a broader role for the brain’s cholinergic system in social learning. Previous research has shown that acetylcholine is important for learning from others, and that damage to cholinergic neurons in the basal forebrain impairs social memory. This study extends that work by showing that increasing acetylcholine activity pharmacologically—either by inhibiting its breakdown or through CBD treatment—can enhance social memory.

There are some limitations to the study. The experiments were conducted in healthy young male mice, and it is unclear whether the same effects would be seen in female mice, older animals, or animals with cognitive impairments. The researchers also used only one dose of CBD and did not examine whether lower or higher doses would have different effects. Finally, while the study shows that muscarinic receptors are involved, it does not identify which specific receptor subtypes are responsible for the observed changes.

Future research could explore how CBD affects cholinergic signaling in more detail, including whether it acts directly on acetylcholine receptors or indirectly by altering enzyme activity. It would also be important to test whether these effects can be reproduced in animal models of cognitive disorders or in humans.

The study, “Cannabidiol enhances socially transmitted food preference: a role of acetylcholine in the mouse basal forebrain,” was authored by Chih-Yu Chang, Wen Dai, and Sherry Shu-Jung Hu.