Alzheimer’s

Oral THC: CBD Cannabis Extract In Main Symptoms Of Alzheimer Disease: Agitation And Weight Loss

Beniamino Palmieri, Maria Vadalà MsC (May 2022)

Ten million new cases of dementia are recorded annually worldwide, with agitation and idiopathic weight loss being the most common symptoms. Several pharmacological therapies have emerged in recent years, but the clinical use of cannabis extracts in older patients with AD is constantly growing. This retrospective, analytical, observational, spontaneous trial aimed to enhance the clinical action of THC: CBD cannabis extract administration in AD patients with severe symptoms such as agitation, weight loss, cognitive impairment, and sleep disturbance.

The NPI-Q demonstrated a reduction (p<0.0001) in agitation, apathy, irritability, sleep disturbances, and eating disturbances, consequently improving caregiver distress. Levels of physically and verbally aggressive behaviours, measured using the CMAI questionnaire, were lower (p<0.0001) in all patients. The MMSSE questionnaire confirmed a significant decrease (p<0.0001) in cognitive impairment in 45% of the patients.

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Effect Of Cannabidiol On The Neural Glyoxalase Pathway Function And Longevity Of Several C. Elegans Strains Including A C. Elegans Alzheimer’s Disease Model

Joel Frandsen, Prabagaran Narayanasamy (April 2022)

Cannabidiol is a nonpsychoactive phytocannabinoid produced by the Cannabis sativa plant and possesses a wide range of pharmacological activities, including anti-inflammatory, antioxidant, and neuroprotective activities. Cannabidiol functions in a neuroprotective manner, in part through the activation of cellular antioxidant pathways. The glyoxalase pathway detoxifies methylglyoxal, a highly reactive metabolic byproduct that can accumulate in the brain, and contributes to the severity of neurodegenerative diseases, including Alzheimer’s disease. While cannabidiol’s antioxidant properties have been investigated, it is currently unknown how it may modulate the glyoxalase pathway. In this research paper, we examine the effects of Cannabidiol on cerebellar neurons and in several Caenorhabditis elegans strains. We determined that a limited amount of Cannabidiol can prevent methylglyoxal-mediated cellular damage through enhancement of the neural glyoxalase pathway and extend the lifespan and survival of C. elegans, including a transgenic C. elegans strain modeling Alzheimer’s disease.

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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.

Cannabidiol Protects Against Alzheimer’s Disease In C. Elegans Via ROS Scavenging Activity Of Its Phenolic Hydroxyl Groups

Yue Zhang, Hongyuan Li, Sha Jin, Yuyuan Lu, Yinghua Peng, Lihui Zhao, Xiaohui Wang (March 2022)

Recent discoveries have implicated the potential of Cannabidiol (CBD) in the prevention of Alzheimer's disease (AD). However, how CBD affects such neurodegenerative disorders remains unclear. Herein, Caenorhabditis elegans (C. elegans) was used as the model organism to elucidate the mechanism by which CBD ameliorates AD in vivo. CBD was found to alleviate the progression of Aβ-induced AD but not tau protein-induced AD or α-syn-induced Parkinson's disease. CBD inhibited the aggregation of Aβ in C. elegans.

These studies show that CBD protects against AD in C. elegans via the ROS scavenging activity of its phenolic hydroxyl groups, which provides insight for further structure-activity relationship studies of CBD as an AD therapeutic.

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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.

Destabilization Of The Alzheimer’s Amyloid-β Protofibrils By THC: A Molecular Dynamics Simulation Study

Pavan Krishna Kanchi, Ashok Kumar Dasmahapatra (March 2021)

Alzheimer’s disease is a leading cause of dementia in the elderly population for which there is no cure at present. Deposits of neurotoxic plaques are found in the brains of patients which are composed of fibrils of the amyloid-β peptide. Molecules which can disrupt these fibrils have gained attention as potential therapeutic agents. Δ-tetrahydrocannabidiol (THC) is a cannabinoid, which can bind to the receptors in the brain, and has shown promise in reducing the fibril content in many experimental studies. In our present study, by employing all atom molecular dynamics simulations, we have investigated the mechanism of the interaction of the THC molecules with the amyloid-β protofibrils. Our results show that the THC molecules disrupt the protofibril structure by binding strongly to them. The driving force for the binding was the hydrophobic interactions with the hydrophobic residues in the fibrils. As a result of these interactions, the tight packing of the hydrophobic core of the protofibrils was made loose, and salt bridges, which were important for stability were disrupted. Hydrogen bonds between the chains of the protofibrils which are important for stability were disrupted, as a result of which the β-sheet content was reduced. The destabilization of the protofibrils by the THC molecules leads to the conclusion that THC molecules may be considered for the therapy in treating Alzheimer’s disease.

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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.

Medical Cannabis For The Treatment Of Dementia: A Review Of Clinical Effectiveness And Guidelines

Kwakye Peprah and Suzanne McCormack (September 2019)

Overall, limited evidence from the studies3,10 included this report suggested that medical cannabis may be effective for treating neuropsychiatric symptoms associated with dementia (i.e., agitation, disinhibition, irritability, aberrant motor behaviour, nocturnal behaviour disorders, and aberrant vocalization and resting care). There was also limited evidence of improvement in rigidity and cognitive scores as assessed by MMSE. However, the data were inconclusive, given the limitations previously discussed. Key sources of uncertainty included the low quality of evidence in the primary studies of the systematic review3 and the fact that the uncontrolled before-and-after study10 was a nonrandomized pilot study in 10 dementia patients that reported descriptive outcomes without statistical analysis. Given these limitations, there is a need for a well-designed randomized controlled trial to confirm the effectiveness of medical cannabis for the treatment of dementia using different formulations that explore varieties of routes of administration.

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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.

Efficacy Of Cannabinoids In A Pre-Clinical Drug-Screening Platform For Alzheimer’s Disease

David Schubert, Devin Kepchia, Zhibin Liang, Richard Dargusch, Joshua Goldberg and Pamela Maher (May 2019)

Here, we determine if a number of non-psychoactive cannabinoids are neuroprotective in a novel pre-clinical AD and neurodegeneration drug-screening platform that is based upon toxicities associated with the aging brain. This drug discovery paradigm has yielded several compounds in or approaching clinical trials for AD. Eleven cannabinoids were assayed for neuroprotection in assays that recapitulate proteotoxicity, loss of trophic support, oxidative stress, energy loss, and inflammation. These compounds were also assayed for their ability to remove intraneuronal amyloid and subjected to a structure-activity relationship analysis.

Important Notice

If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.

Cannabis Therapeutics And The Future of Neurology

Ethan B. Russo  (October 2018)

Recent reviews (Aso and Ferrer, 2014; Ahmed et al., 2015) have nicely summarized the pathophysiology of AD: a neurodegenerative disease with senile plaques formed of fibrillar β-amyloid (Aβ) from cleavage of the Aβ precursor protein (APP) by β- and γ-secretases and by presence of neurofibrillary tangles composed of hyper-phosphorylated and nitrated tau protein. The latter precedes Aβ deposition in sporadic cases. Once the process begins, deterioration is inexorable. Additional pathology includes functional mitochondrial defects, increased reactive oxygen species (ROS) and reactive nitrogen species (RNS), and failure of enzymes involved in energy production that, in turn, produces nerve cell exhaustion. Eventually, synapses and dendritic branching fail, with consequent progressive neuronal wastage. Dementia and cognitive decline develop, and no treatment arrests the process. Intervention must begin at an early preclinical stage to have any hope of success. Endocannabinoid function modulates the primary pathological processes of AD during the silent phase of neurodegeneration: protein misfolding, neuroinflammation, excitotoxicity, mitochondrial dysfunction and oxidative stress. CB2 levels increase in AD especially in microglia around senile plaques, and its stimulation stimulates Aβ removal by macrophages.

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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.

Cannabidiol Reverses Deficits In Hippocampal LTP In A Model Of Alzheimer’s Disease

Blathnaid Hughes (March 2018)

Here we demonstrate for the first time that cannabidiol (CBD) acts to protect synaptic plasticity in an in vitro model of Alzheimer’s disease (AD). The non-psycho active component of Cannabis sativa, CBD has previously been shown to protect against the neurotoxic effects of beta amyloid peptide (Aβ) in cell culture and cognitive behavioural models of neurodegeneration.

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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.

Innovative Therapeutic Potential Of Cannabinoid Receptors As Targets In Alzheimer’s Disease And Less Well-Known Diseases

JA Paez, NE Campillo  (February 2018)

The endocannabinoid system has been implicated in a wide diversity of biological processes, in both the central and peripheral nervous systems, including memory, learning, neuronal development, stress and emotions, food intake, energy regulation, peripheral metabolism, and the regulation of hormonal balance through the endocrine system. In this context, this article will review the current knowledge of the therapeutic potential of cannabinoid receptor as a target in Alzheimer’s disease and other less well-known diseases that include, among others, multiple sclerosis, bone metabolism, and Fragile X syndrome. The therapeutic applications will be addressed through the study of cannabinoid agonists acting as single drugs and multi-target drugs highlighting the CB2 receptor agonist.

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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.

Receptor-Heteromer Mediated Regulation Of Endocannabinoid Signaling In Activated Microglia. Role Of CB1 and CB2 Receptors And Relevance For Alzheimer’s Disease And Levodopa-Induced Dyskinesia

GemmaNavarro, DasielBorroto-Escuela, EdgarAngelats, ÍñigoEtayo, IreneReyes-Resina, MartaPulido-Salgado, Ana I.Rodríguez-Pérez, Enric I.Canela, JosepSaura, José LuisLanciego, José LuisLabandeira-García, Carlos A.Saura, KjellFuxe, RafaelFranco  (January 2018)

Endocannabinoids are important regulators of neurotransmission and, acting on activated microglia, they are postulated as neuroprotective agents. Endocannabinoid action is mediated by CB1 and CB2 receptors, which may form heteromeric complexes (CB1-CB2Hets) with unknown function in microglia. We aimed at establishing the expression and signaling properties of cannabinoid receptors in resting and LPS/IFN-γ-activated microglia. In activated microglia mRNA transcripts increased (2 fold for CB1 and circa 20 fold for CB2), whereas receptor levels were similar for CB1 and markedly upregulated for CB2; CB1-CB2Hets were also upregulated.

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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.

The Endocannabinoid System Modulating Levels Of Consciousness, Emotions And Likely Dream Contents

Eric Murillo-Rodriguez, Jose Carlos Pastrana-Trejo, Mireille Salas-Crisóstomo, ; Miriel de-la-Cruz  (May 2017)

Cannabinoids are derivatives that are either compounds occurring naturally in the plant, Cannabis sativa or synthetic analogs of these molecules. The first and most widely investigated of the cannabinoids is Δ9-tetrahydrocannabinol (Δ9-THC), which is the main psychotropic constituent of cannabis and undergoes significant binding to cannabinoid receptors. These cannabinoid receptors are seven-transmembrane receptors that received their name from the fact that they respond to cannabinoid compounds, including Δ9-THC.

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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.

The Therapeutic Potential Of The Phytocannabinoid Cannabidiol For Alzheimer’s Disease

Tim Karl, Brett Garner, David Cheng  (April 2017)

Alzheimer’s disease (AD) is the most common neurodegenerative disorder, characterized by progressive loss of cognition. Over 35 million individuals currently have AD worldwide. Unfortunately, current therapies are limited to very modest symptomatic relief. The brains of AD patients are characterized by the deposition of amyloid-β and hyperphosphorylated forms of tau protein. AD brains also show neurodegeneration and high levels of oxidative stress and inflammation. The phytocannabinoid cannabidiol (CBD) possesses neuroprotective, antioxidant and anti-inflammatory properties and reduces amyloid-β production and tau hyperphosphorylation in vitro. CBD has also been shown to be effective in vivo making the phytocannabinoid an interesting candidate for novel therapeutic interventions in AD, especially as it lacks psychoactive or cognition-impairing properties.

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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.

In Vivo Evidence For Therapeutic Properties Of Cannabidiol (CBD) For Alzheimer’s Disease

Georgia Watt and Tim Karl  (February 2017)

Here, we summarize the current status quo of in vivo effects of CBD in established pharmacological and transgenic animal models for AD. The studies demonstrate the ability of CBD to reduce reactive gliosis and the neuroinflammatory response as well as to promote neurogenesis. Importantly, CBD also reverses and prevents the development of cognitive deficits in AD rodent models. Interestingly, combination therapies of CBD and Δ9-tetrahydrocannabinol (THC), the main active ingredient of cannabis sativa, show that CBD can antagonize the psychoactive effects associated with THC and possibly mediate greater therapeutic benefits than either phytocannabinoid alone.

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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.

Endocannabinoids And Neurodegenerative Disorders: Parkinson’s Disease, Huntington’s Chorea, Alzheimer’s Disease, and Others

Javier Fernández-Ruiz, Julián Romero, José A. Ramos  (2015)

This review focuses on the role of the endocannabinoid signaling system in controlling neuronal survival, an extremely important issue to be considered when developing new therapies for neurodegenerative disorders.

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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.