1. In vivo investigations of pharmacological and therapeutic long-term donepezil- JWH-133 co-treatment associations
  2. Neuroimaging evaluation of cerebral metabolism using 18FDG-PET
  3. Histology and immunohistochemistry analysis
  4. Acetylcholine expression and amyloid-β quantification


Alzheimer’s disease (AD) is a major growing health challenge worldwide with up to 80% of all cases of dementia. The etiology of this disease is not completely understood and no safe and effective drug to prevent, stop or reverse its evolution is currently available. CB1 and CB2 endocannabinoid receptors are widely expressed in the central nervous system and it has been found that CB2 type are selectively overexpressed in cells associated with amyloid-β enriched neuritic. Specific CB2 agonists are a promising target for AD therapy due to their lack of psychoactive properties, but are still insufficiently studied. The aim of this project is to evaluate the effects of long-term donepezil-CB2 specific agonist JWH-133 co-treatment in transgenic mice, in pre-symptomatic and early stage of the symptomatic phase of the AD. A complete set of in vivo studies supported by cognitive performance evaluation, multimodal imaging, histology and immunohistochemistry analysis will help accomplish the objectives of this original proposal: investigate the preclinical efficacy of long-term donepezil- JWH-133 co-treatment associations; evaluate the impact of therapy on cerebral metabolism; identify the acetylcholine-related changes and amyloid-β quantification in an animal model. Translating selective CB2 cannabinoids into the clinic is not an easy challenge, but identifying new therapeutic avenues for treating AD holds the promise of improving the quality of life of millions of dementia patients.