Potential and Limits of Cannabinoids in Alzheimer’s Disease Therapy

SIMPLE SUMMARY: This review was aimed at exploring the potentiality of drugging the endocannabinoid system as a therapeutic option for Alzheimer’s disease (AD). Recent discoveries have demonstrated how the modulation of cannabinoid receptor 1 (CB1) and receptor 2 (CB2) can exert neuroprotective effects without the recreational and pharmacological properties of Cannabis sativa. Thus, this review explores the potential of cannabinoids in AD, also highlighting their limitations in perspective to point out the need for further research on cannabinoids in AD therapy. ABSTRACT: Alzheimer’s disease (AD) is a detrimental brain disorder characterized by a gradual cognitive decline and neuronal deterioration. To date, the treatments available are effective only in the early stage of the disease. The AD etiology has not been completely revealed, and investigating new pathological mechanisms is essential for developing effective and safe drugs. The recreational and pharmacological properties of marijuana are known for centuries, but only recently the scientific community started to investigate the potential use of cannabinoids in AD therapy—sometimes with contradictory outcomes. Since the endocannabinoid system (ECS) is highly expressed in the hippocampus and cortex, cannabis use/abuse has often been associated with memory and learning dysfunction in vulnerable individuals. However, the latest findings in AD rodent models have shown promising effects of cannabinoids in reducing amyloid plaque deposition and stimulating hippocampal neurogenesis. Beneficial effects on several dementia-related symptoms have also been reported in clinical trials after cannabinoid treatments. Accordingly, future studies should address identifying the correct therapeutic dosage and timing of treatment from the perspective of using cannabinoids in AD therapy. The present paper aims to summarize the potential and limitations of cannabinoids as therapeutics for AD, focusing on recent pre-clinical and clinical evidence.