Please use this link to access this publication. Abstract Introduction Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of aging (70%). Neuropsychiatric symptoms (NPS) in AD are a major cause of burden to patients, caregivers, and society and are near-universal at some point in the AD course (97%). One of the most troubling NPS is agitation (Agit-AD), typified by a variety of problem behaviors including combativeness, yelling, pacing, lack of cooperation with care, insomnia, and restlessness. Neurobiological mechanisms that contribute to Agit-AD include brain atrophy, degradation of neurotransmission, neuroinflammation, disrupted circadian rhythms, comorbidities, and frailty. There is a great need for better interventions that target Agit-AD, which is a major source...

Please use this link to access this publication. Abstract Agitation is a common complication of Alzheimer’s dementia (Agit-AD) associated with substantial morbidity, high healthcare service utilization, and adverse emotional and physical impact on care partners. There are currently no FDA-approved pharmacological treatments for Agit-AD. We present the study design and baseline data for an ongoing multisite, three-week, double-blind, placebo-controlled, randomized clinical trial of dronabinol (synthetic tetrahydrocannabinol [THC]), titrated to a dose of 10 mg daily, in 80 participants to examine the safety and efficacy of dronabinol as an adjunctive treatment for Agit-AD. Preliminary findings for 44 participants enrolled thus far show a predominately female,...

Abstract A hallmark of Alzheimer’s disease (AD) is the accumulation of tau protein in the brain. Compelling evidence indicates that the presence of tau aggregates causes irreversible neuronal destruction, eventually leading to synaptic loss. So far, the inhibition of tau aggregation has been recognized as one of the most effective therapeutic strategies. Cannabidiol (CBD), a major component found in Cannabis sativa L., has antioxidant activities as well as numerous neuroprotective features. Therefore, we hypothesize that CBD may serve as a potent substance to hamper tau aggregation in AD. In this study, we aim to investigate the CBD effect on the aggregation of recombinant human...

Abstract Background With the rising prevalence as the main cause of dementia, Alzheimer’s disease (AD) is emerging as one of the most important medical and social challenges for the healthcare system in both developed and developing countries. Despite significant advancement in our understanding of AD and improvement in therapeutic modalities for AD patients, however, there is currently a marked lack of definitive and effective treatment for AD. Therefore, there is an exigent need for an alternative therapy to treat the underlying causes of AD rather than its symptomatic effects. Cannabidiol (CBD) is a safe, non-psychoactive phytocannabinoid produced by cannabis plant. Increasing evidence from our...

Please use this link to access this publication. Abstract The aberrant accumulation of disease-specific protein aggregates accompanying cognitive decline is a pathological hallmark of age-associated neurological disorders, also termed as proteinopathies, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and multiple sclerosis. Along with oxidative stress and neuroinflammation, disruption in protein homeostasis (proteostasis), a network that constitutes protein surveillance system, plays a pivotal role in the pathobiology of these dementia disorders. Cannabidiol (CBD), a non-psychotropic phytocannabinoid of Cannabis sativa, is known for its pleiotropic neuropharmacological effects on the central nervous system, including the ability to abate oxidative stress, neuroinflammation, and protein misfolding....

Please use this link to access this publication. Abstract: There is a dire need for due innovative therapeutic modalities to improve outcomes of AD patients. In this study, we tested whether cannabidiol (CBD) improves outcomes in a translational model of familial AD and to investigate if CBD regulates interleukin (IL)-33 and triggering receptor expressed on myeloid cells 2 (TREM2), which are associated with improved cognitive function. CBD was administered to 5xFAD mice, which recapitulate early onset, familial AD. Behavioral tests and immunoassays were used to evaluate cognitive and motor outcomes. Our findings suggest that CBD treatment enhanced IL-33 and TREM2 expression, ameliorated the symptoms...

Abstract Alzheimer’s disease (AD), the most common neurodegenerative disease, is characterized by progressive cognitive impairment. The deposition of amyloid beta (Aβ) and hyperphosphorylated tau is considered the hallmark of AD pathology. Many therapeutic approaches such as Food and Drug Administration-approved cholinesterase inhibitors and N–methyl–D–aspartate receptor antagonists have been used to intervene in AD pathology. However, current therapies only provide limited symptomatic relief and are ineffective in preventing AD progression. Cannabidiol (CBD), a phytocannabinoid devoid of psychoactive responses, provides neuroprotective effects through both cannabinoid and noncannabinoid receptors. Recent studies using an AD mouse model have suggested that CBD can reverse cognitive deficits along with Aβ-induced...

Abstract Background The use of cannabidiol (CBD) has grown rapidly over the last few years. CBD has been purported to work on a range of conditions, including anxiety, pain, and psychosis. There has been recent interest in CBD as a treatment for age-related cognitive disorders due to its antioxidant and anti-inflammatory properties. Method Here, we tested the effects of chronic CBD administration on learning and memory in the SAMP8 mouse model of Alzheimer’s disease. SAMP8 mice develop an age-related impairment in learning and memory which corresponds to an increase in amyloid-β (Aβ), hyperphosphorylated tau, oxidative stress, impaired efflux of Aβ across the blood-brain barrier...

Abstract As the major nonpsychotropic constituent of Cannabis sativa, cannabidiol (CBD) is regarded as one of the most promising therapeutic agents due to its proven effectiveness in clinical trials for many human diseases. Due to the urgent need for more efficient pharmacological treatments for several chronic diseases, in this review, we discuss the potential beneficial effects of CBD for Alzheimer’s disease, epilepsy, multiple sclerosis, and neurological cancers. Due to its wide range of pharmacological activities (e.g., antioxidant, anti-inflammatory, and neuroprotective properties), CBD is considered a multimodal drug for the treatment of a range of neurodegenerative disorders, and various cancer types, including neoplasms of the...

Please use this link to access this publication. Abstract Alzheimer's disease (AD) is a central nervous system disease characterized by dementia, which has now become a major threat to global health. Cannabidiol (CBD) is a natural component extracted from the hemp plant and exhibits multiple mechanisms to improve the pathological process of AD in vitro and in vivo. However, its underlying molecular mechanism is still unclear. This study attempts to reveal its common mechanism through transcriptome sequence. We performed transcriptome sequence in the hippocampus of 6 month old APP/PS1 mice chronically treated with CBD for one month or 30 days. In addition, Aβ plaques...