Efficacy of Cannabinoids in a Pre-Clinical Drug-Screening Platform for Alzheimer’s Disease

Schubert, David; Kepchia, Devin; Liang, Zhibin; Dargusch, Richard; Goldberg, Joshua; Maher, Pamela

doi:10.1007/s12035-019-1637-8

Cited by 64 publications

(75 citation statements)

References 61 publications

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“…In vitro , Schubert et al (2019) reported that CBG (100 nM) prevented MC65 neurons from accumulating toxic amyloid β (Aβ) protein in an Alzhiemer's disease model. CBG also preserved neuronal trophic factors in primary rat cortical neurons (EC 50 1.5 μM) and prevented oxytosis in mouse HT22 hippocampal nerve cells (EC 50 1.9 μM).…”

Section: Resultsmentioning

confidence: 99%

A systematic review of minor phytocannabinoids with promising neuroprotective potential

Stone

Murphy

England

et al. 2020

British J Pharmacology

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Embase and PubMed were systematically searched for articles addressing the neuroprotective properties of phytocannabinoids, apart from cannabidiol and Δ9‐tetrahydrocannabinol, including Δ9‐tetrahydrocannabinolic acid, Δ9‐tetrahydrocannabivarin, cannabidiolic acid, cannabidivarin, cannabichromene, cannabichromenic acid, cannabichromevarin, cannabigerol, cannabigerolic acid, cannabigerivarin, cannabigerovarinic acid, cannabichromevarinic acid, cannabidivarinic acid, and cannabinol. Out of 2,341 studies, 31 articles met inclusion criteria. Cannabigerol (range 5 to 20 mg·kg−1) and cannabidivarin (range 0.2 to 400 mg·kg−1) displayed efficacy in models of Huntington's disease and epilepsy. Cannabichromene (10–75 mg·kg−1), Δ9‐tetrahydrocannabinolic acid (20 mg·kg−1), and tetrahydrocannabivarin (range 0.025–2.5 mg·kg−1) showed promise in models of seizure and hypomobility, Huntington's and Parkinson's disease. Limited mechanistic data showed cannabigerol, its derivatives VCE.003 and VCE.003.2, and Δ9‐tetrahydrocannabinolic acid mediated some of their effects through PPAR‐γ, but no other receptors were probed. Further studies with these phytocannabinoids, and their combinations, are warranted across a range of neurodegenerative disorders.

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Section: Resultsmentioning

confidence: 99%

A systematic review of minor phytocannabinoids with promising neuroprotective potential

Stone

Murphy

England

et al. 2020

British J Pharmacology

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“…THC reduced the fluorescence intensity in the thioflavin test in a dose-dependent manner by direct interaction with the Aβ peptide [ 63 ], affecting Aβ fibril formation and aggregation [ 64 ]. THC stimulates the removal of intracellular Aβ and blocks the inflammatory response [ 65 , 66 ]. THC has been shown to inhibit the enzyme acetylcholinesterase (AChE) activity more effectively than the approved drugs for AD treatment—donepezil and tacrine [ 67 ].…”

Section: Cannabinoids and Endocannabinoid Systemsmentioning

confidence: 99%

Potential and Limits of Cannabinoids in Alzheimer’s Disease Therapy

Abate

Uberti

Tambaro

2021

Biology

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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.

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“…The key role of cannabinoid receptors in AD makes cannabinoids and cannabis extracts a potential therapeutic candidate for AD [ 28 , 29 , 30 ]. AD is a progressive degenerative disease of the brain.…”

Section: Introductionmentioning

confidence: 99%

Attenuation of Oxidative Stress by Cannabinoids and Cannabis Extracts in Differentiated Neuronal Cells

Raja

Ahmadi

Costa³

et al. 2020

Pharmaceuticals

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In this proof-of-concept study, the antioxidant activity of phytocannabinoids, namely cannabidiol (CBD) and Δ9- tetrahydrocannabinol (THC), were investigated using an in vitro system of differentiated human neuronal SY-SH5Y cells. The oxidative stress was induced by hydrogen peroxide, as reactive oxygen species (ROS). Alzheimer’s disease (AD)-like pathological conditions were mimicked in vitro by treating the differentiated neuronal cells with amyloid-β1–42 (Aβ1–42) in the presence of Cu(II). We showed that THC had a high potency to combat oxidative stress in both in vitro models, while CBD did not show a remarkable antioxidant activity. The cannabis extracts also exhibited a significant antioxidant activity, which depended on the ratio of the THC and CBD. However, our results did not suggest any antagonist effect of the CBD on the antioxidant activity of THC. The effect of cannabis extracts on the cell viability of differentiated human neuronal SY-SH5Y cells was also investigated, which emphasized the differences between the bioactivity of cannabis extracts due to their composition. Our preliminary results demonstrated that cannabis extracts and phytocannabinoids have a promising potential as antioxidants, which can be further investigated to develop novel pharmaceuticals targeting oxidative stress therapy.

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Efficacy of Cannabinoids in a Pre-Clinical Drug-Screening Platform for Alzheimer’s Disease

Cited by 64 publications

References 61 publications

A systematic review of minor phytocannabinoids with promising neuroprotective potential

A systematic review of minor phytocannabinoids with promising neuroprotective potential

Potential and Limits of Cannabinoids in Alzheimer’s Disease Therapy

Attenuation of Oxidative Stress by Cannabinoids and Cannabis Extracts in Differentiated Neuronal Cells

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