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The Therapeutic Use of Cannabinoids in Neurodegenerative Disorders
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The Therapeutic Use of Cannabinoids in Neurodegenerative Disorders

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Neuroscience".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 18084

Special Issue Editor

Dr. Simone Tambaro

E-Mail Website
Guest Editor
Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, 171 64 Solna, Sweden
Interests: endocannabinoid system; Alzheimer’s; amyloid; inflammation; microglia; animal models; transmembrane proteins
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The recreational and pharmacological properties of cannabis (or marijuana) have been known for centuries. However, only in the last several decades has the scientific community started to investigate the therapeutic use of cannabinoids in neurodegenerative disorders like Alzheimer's (AD) and Parkinson's disease (PD). Cannabis has been observed to affect different brain processes in particular, due to the high numbers of cannabinoid receptors in the hippocampus, influencing memory and learning processes. Several studies also reported that cannabinoids have neuroprotective and anti-neuroinflammatory properties. To date, evidence of the beneficial effects of cannabinoids in AD and PD therapy is contradictory, where long-term effects on memory and learning seem to change according to the age of the user and the dose. However, positive results in AD animal models and in humans have been described using low doses of THC, cannabinol, and other synthetic compounds. Recent findings have shown an effect of cannabinoids in reducing plaque deposition and stimulating hippocampal neurogenesis. Cannabis exposure has also been linked to a reduction of bradykinesia and/or tremors in PD animal models; a similar response has been reported in patients.

These results provide an incentive to further explore the use of cannabinoids as a potential therapeutic approach for AD and PD treatment. However, much more research is needed to reveal any potential benefits and side effects.

This Special Issue welcomes submissions of original research articles, reviews, and short communications focusing on the mechanisms underlying the curative properties of natural and synthetic cannabinoids in neurodegenerative brain disorders. This Issue will certainly increase our understanding of the benefits and risks of marijuana components as a treatment for patients with AD and PD.

Dr. Simone Tambaro
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cannabis
  • Alzheimer’s
  • Parkinson’s
  • inflammation
  • THC
  • cannabinol
  • neurodegeneration
  • endocannabinoid system
  • amyloid
  • animal models

Published Papers (3 papers)

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Research

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22 pages, 3278 KiB  
Article
Imbalance of Endocannabinoid/Lysophosphatidylinositol Receptors Marks the Severity of Alzheimer’s Disease in a Preclinical Model: A Therapeutic Opportunity
by Dina Medina-Vera, Cristina Rosell-Valle, Antonio J. López-Gambero, Juan A. Navarro, Emma N. Zambrana-Infantes, Patricia Rivera, Luis J. Santín, Juan Suarez and Fernando Rodríguez de Fonseca
Biology 2020, 9(11), 377; https://doi.org/10.3390/biology9110377 - 05 Nov 2020
Cited by 21 | Viewed by 3140
Abstract
Alzheimer’s disease (AD) is the most common form of neurodegeneration and dementia. The endocannabinoid (ECB) system has been proposed as a novel therapeutic target to treat AD. The present study explores the expression of the ECB system, the ECB-related receptor GPR55, and cognitive [...] Read more.
Alzheimer’s disease (AD) is the most common form of neurodegeneration and dementia. The endocannabinoid (ECB) system has been proposed as a novel therapeutic target to treat AD. The present study explores the expression of the ECB system, the ECB-related receptor GPR55, and cognitive functions (novel object recognition; NOR) in the 5xFAD (FAD: family Alzheimer’s disease) transgenic mouse model of AD. Experiments were performed on heterozygous (HTZ) and homozygous (HZ) 11 month old mice. Protein expression of ECB system components, neuroinflammation markers, and β-amyloid (Aβ) plaques were analyzed in the hippocampus. According to the NOR test, anxiety-like behavior and memory were altered in both HTZ and HZ 5xFAD mice. Furthermore, both animal groups displayed a reduction of cannabinoid (CB1) receptor expression in the hippocampus, which is related to memory dysfunction. This finding was associated with indirect markers of enhanced ECB production, resulting from the combination of impaired monoacylglycerol lipase (MAGL) degradation and increased diacylglycerol lipase (DAGL) levels, an effect observed in the HZ group. Regarding neuroinflammation, we observed increased levels of CB2 receptors in the HZ group that positively correlate with Aβ’s accumulation. Moreover, HZ 5xFAD mice also exhibited increased expression of the GPR55 receptor. These results highlight the importance of the ECB signaling for the AD pathogenesis development beyond Aβ deposition. Full article
(This article belongs to the Special Issue The Therapeutic Use of Cannabinoids in Neurodegenerative Disorders)
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Review

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34 pages, 1566 KiB  
Review
Endocannabinoid Modulation in Neurodegenerative Diseases: In Pursuit of Certainty
by Alexandru Vasincu, Răzvan-Nicolae Rusu, Daniela-Carmen Ababei, Mădălina Larion, Walther Bild, Gabriela Dumitrița Stanciu, Carmen Solcan and Veronica Bild
Biology 2022, 11(3), 440; https://doi.org/10.3390/biology11030440 - 14 Mar 2022
Cited by 14 | Viewed by 3538
Abstract
Neurodegenerative diseases are an increasing cause of global morbidity and mortality. They occur in the central nervous system (CNS) and lead to functional and mental impairment due to loss of neurons. Recent evidence highlights the link between neurodegenerative and inflammatory diseases of the [...] Read more.
Neurodegenerative diseases are an increasing cause of global morbidity and mortality. They occur in the central nervous system (CNS) and lead to functional and mental impairment due to loss of neurons. Recent evidence highlights the link between neurodegenerative and inflammatory diseases of the CNS. These are typically associated with several neurological disorders. These diseases have fundamental differences regarding their underlying physiology and clinical manifestations, although there are aspects that overlap. The endocannabinoid system (ECS) is comprised of receptors (type-1 (CB1R) and type-2 (CB2R) cannabinoid-receptors, as well as transient receptor potential vanilloid 1 (TRPV1)), endogenous ligands and enzymes that synthesize and degrade endocannabinoids (ECBs). Recent studies revealed the involvement of the ECS in different pathological aspects of these neurodegenerative disorders. The present review will explore the roles of cannabinoid receptors (CBRs) and pharmacological agents that modulate CBRs or ECS activity with reference to Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Huntington’s Disease (HD) and multiple sclerosis (MS). Full article
(This article belongs to the Special Issue The Therapeutic Use of Cannabinoids in Neurodegenerative Disorders)
21 pages, 1215 KiB  
Review
Potential and Limits of Cannabinoids in Alzheimer’s Disease Therapy
by Giulia Abate, Daniela Uberti and Simone Tambaro
Biology 2021, 10(6), 542; https://doi.org/10.3390/biology10060542 - 17 Jun 2021
Cited by 34 | Viewed by 10430
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue The Therapeutic Use of Cannabinoids in Neurodegenerative Disorders)
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