Cannabinoid-Based Drug Restores Memory in Neurodegeneration Models
Cannabinoid receptor targeting restores memory in early neurodegeneration.

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Research led by the University of the Basque Country (UPV/EHU) has identified a potential therapeutic pathway involving cannabinoid receptors to counter memory impairment in early stages of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. The findings, which emerge from over two decades of research, suggest that targeting specific neurotransmitter systems could enhance cognitive function in affected individuals.
Cannabinoid receptors
Proteins located on the surface of cells that interact with cannabinoids, either those produced naturally by the body or from external sources, to regulate processes such as pain, mood, appetite, and memory.The research team focused on the interplay between the cholinergic and cannabinoid systems in the brain. While the cholinergic system, critical for learning and memory, experiences early degeneration, the cannabinoid system initially responds with a protective mechanism. However, as the disease progresses, this system also deteriorates, presenting an opportunity for therapeutic intervention.
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Subscribe for FREE“Analyses carried out over the years on a very large sample of brain tissue from autopsies of patients who were at different stages of development of the disease enabled us, intriguingly, to see that when the first clinical symptoms of Alzheimer's emerge, damage is found in the area that is initially affected in patients and is caused by one of the interneuronal transmission systems, the cholinergic system (which controls memory and learning and uses acetylcholine as a neurotransmitter); by contrast, we saw that another neurotransmission system, the cannabinoid system, increases”
Dr. Rodríguez-Puertas.
Cholinergic system
A network in the brain that uses acetylcholine as a neurotransmitter and plays a crucial role in learning, memory, and attention.Testing a cannabinoid drug in disease models
The study explored the impact of WIN55.212-2, a synthetic compound targeting cannabinoid receptors, in rodent models mimicking early stages of neurodegeneration. Treated animals exhibited restored spatial learning and memory abilities comparable to healthy controls. This result suggests that cannabinoid receptor activation can mitigate damage to cholinergic pathways.
"They behaved in the same way as those without brain damage: they learned and remembered spatial orientation in the same way. You could say that in some way the drug reversed the damage or protected the brain.”
Dr. Marta Moreno.
Lipid-based mechanisms behind cognitive improvement
The researchers employed advanced lipidomic techniques developed at UPV/EHU to pinpoint biochemical changes in the brain. These methods allowed for precise identification and localization of lipids. Results revealed that cannabinoid receptor activation stimulated the production of choline-containing lipids, precursors to acetylcholine, a neurotransmitter vital for memory. Additionally, the activity of damaged cholinergic neuronal receptors was restored, further contributing to cognitive recovery.
Lipidomics
The large-scale study of pathways and networks of cellular lipids in biological systems, which provides insights into their role in health and disease.Challenges in drug development and future steps
Despite promising preclinical findings, the molecule used in the study, WIN55.212-2, poses challenges for further development. Its widespread use in research and lack of commercial exclusivity make it unattractive for pharmaceutical investment in toxicology studies or clinical trials. To overcome this hurdle, the team is working with collaborators to develop structurally similar molecules with commercial viability.
Reference: Moreno‐Rodríguez M, Martínez‐Gardeazabal J, Bengoetxea De Tena I, et al. Cognitive improvement via cortical cannabinoid receptors and choline‐containing lipids. British J Pharmacology. 2025;182(4):1038-1058. doi: 10.1111/bph.17381
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