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Evaluation of Neuromodulatory Effects of Cannabidiol in Alzheimer’s Disease using Brain Imaging Markers: A Systematic Literature Review

Teddy Salan
University of Miami

Co-Authors: Christian Camargo1, Suresh Pallikkuth1, Yan Wang2, Varan Govind1
1University of Miami, 2University of Florida

Background: Among various mechanisms implicated in the etiology of Alzheimer’s disease (AD), neuroinflammation, oxidative stress, and disruption of the endocannabinoid (ECS) system, play key roles in the disease onset and progression. Numerous human and animal model in vivo studies have demonstrated the potential of cannabis-based products in modulating these processes, specifically cannabidiol (CBD), due to its anti-inflammatory, anti-oxidative, ECS modulatory, and neuroprotective properties. However, it is unclear how many studies have used neuro-imaging techniques to examine the effects of CBD on the above processes in the brains of AD patients in vivo.

Objective: To perform a systematic literature review to summarize the impact of CBD treatment in the brains of AD patients using neuroimaging methods.

Methods: A PubMed literature search containing the terms “Alzheimer’s disease”, combined with “cannabidiol”, “cannabinoid”, “cannabis”, or “marijuana” and with “MRI” or “PET” was performed.

Results: The literature search identified 32 articles. None of these articles investigated marijuana or its products or their effects on the brains of patients with AD. Therefore, to the best of our knowledge, there are no published studies that investigated the effects of CBD in the brains of patients with AD using brain imaging methods (i.e., MRI and PET). However, there are two brain MRI and three PET studies that evaluated the effects of CBD on AD-relevant brain structures (e.g., hippocampus) and function in healthy human subjects or animal models. MRI: One study using arterial spin labeling MRI showed that CBD increased cerebral blood flow in healthy subjects and associated with improved reaction time and working memory, particularly in the hippocampus and other brain structures affected by AD. Another study using structural MRI showed that CBD treatment in cannabis consumers restored the hippocampal structure, as evidence of the differential effect of CBD compared to other cannabis compounds. PET: Three studies evaluated the use of cannabinoids in AD animal models; one showed that CBD improved fluorodeoxyglucose metabolism and memory, and two studies showed that synthetic cannabinoids (WIN-55-212-2 and JWH-133) reduced TNF-α expression and β-amyloid levels.

Conclusions: Despite CBD showing promising results in restoring hippocampal structure and function and reducing neuroinflammation in the brains of healthy subjects, evidence-based knowledge on the effects of CBD on the brains of AD patients using advanced in vivo MRI techniques is still lacking. Future studies should focus on filling this knowledge gap and gather comprehensive brain imaging data in AD patients who are taking cannabis products.