Dementia & Alzheimer's Disease

Best reviews

2021: This review takes a deep dive into the data on CBD for Alzheimer’s disease

Understanding the Modulatory Effects of Cannabidiol on Alzheimer’s Disease

https://www.mdpi.com/2076-3425/11/9/1211

2021: This review looks at using PEA to treat cognitive dysfunction syndrome in pets (a model of Alzheimer’s)

Successful and Unsuccessful Brain Aging in Pets: Pathophysiological Mechanisms behind Clinical Signs and Potential Benefits from Palmitoylethanolamide Nutritional Intervention

https://www.mdpi.com/2076-2615/11/9/2584

2021: This review looks at how the endocannabinoid system forms a bridge between Alzheimer’s disease & the gut microbiome

The Endocannabinoid System: A Bridge between Alzheimer’s Disease and Gut Microbiota

https://www.mdpi.com/2075-1729/11/9/934

2021: This review looks at how lowering the activation of endocannabinoid signaling in the brain’s microglia (immune cells) lessens the neuroinflammation of Alzheimer’s disease

Potentiation of microglial endocannabinoid signaling alleviates neuroinflammation in Alzheimer's disease

https://pubmed.ncbi.nlm.nih.gov/34508923/

2021: A review of targeting the CB2 receptor for Alzheimer’s disease

Cannabinoid receptor 2 selective agonists and Alzheimer's disease: An insight into the therapeutic potentials

https://pubmed.ncbi.nlm.nih.gov/34486749/

2021: A review of 15 studies using cannabinoids for dementia

Medical cannabinoids for treatment of neuropsychiatric symptoms in dementia: systematic review

https://pubmed.ncbi.nlm.nih.gov/34374269/

2021: This review looks at targeting FAAH & MAGL to treat Alzheimer’s disease

The role of endocannabinoid pathway in the neuropathology of Alzheimer's disease: Can the inhibitors of MAGL and FAAH prove to be potential therapeutic targets against the cognitive impairment associated with Alzheimer's disease?

https://pubmed.ncbi.nlm.nih.gov/34217798/

2021: This review suggests the cannabinoids as uniquely suited to treating the dysfunctions of Alzheimer’s disease

The therapeutic benefits of natural cannabinoids in delaying the pathophysiology of Alzheimer's disease

https://rsdjournal.org/index.php/rsd/article/view/15418

2020: A new meta-review find that THC & CBD both inhibit the progression of Alzheimer's plaques in animal models

Impact of Cannabis-Based Medicine on Alzheimer's disease by Focusing on the Amyloid β- Modifications: A Systematic Study

https://pubmed.ncbi.nlm.nih.gov/32640965/

2020: A review of using THC & CBD for Alzheimer's

A Review on Studies of Marijuana for Alzheimer’s Disease – Focusing on CBD, THC

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970569/

2020: A meta-review of the alterations to the ECS that occur in Alzheimer's (22 studies)

Endocannabinoid system alterations in Alzheimer's disease: a systematic review of human studies

https://pubmed.ncbi.nlm.nih.gov/32980333/

2020: The endocannabinoids interact with the muscarinic acetylcholine receptor (on which Aminatas mushrooms work) and this might be helpful Alzheimer's

Crosstalk between the M1 muscarinic acetylcholine receptor and the endocannabinoid system: A relevance for Alzheimer's disease?

https://www.ncbi.nlm.nih.gov/pubmed/31978506

2020: Cannabinoids for the pain & neural alterations of Alzheimer's disease

Emerging Promise of Cannabinoids for the Management of Pain and Associated Neuropathological Alterations in Alzheimer's Disease

https://pubmed.ncbi.nlm.nih.gov/32792944/

2020: A review of the use of cannabinoids for the neuropsychiatric symptoms of Alzheimer's disease

Cannabinoids for the Neuropsychiatric Symptoms of Dementia: A Systematic Review and Meta-Analysis

https://pubmed.ncbi.nlm.nih.gov/31835954/

2020: A review of how CBD protects in epilepsy & Alzheimer’s

Overview of cannabidiol (CBD) and its analogues: Structures, biological activities, and neuroprotective mechanisms in epilepsy and Alzheimer's disease

https://www.ncbi.nlm.nih.gov/pubmed/32109623

2019: A review of the safety & efficacy of cannabinoids for dementia

Safety and effectiveness of cannabinoids for the treatment of neuropsychiatric symptoms in dementia: a systematic review

https://pubmed.ncbi.nlm.nih.gov/31205674/

2019: A review of the trials of cannabinoids for dementia

Effectiveness of Cannabinoids for Treatment of Dementia: A Systematic Review of Randomized Controlled Trials

https://pubmed.ncbi.nlm.nih.gov/32186469/

2019: Cannabinoids for the agitation and aggression of Alzheimer's disease

Natural and Synthetic Cannabinoids for Agitation and Aggression in Alzheimer's Disease: A Meta-Analysis

https://pubmed.ncbi.nlm.nih.gov/30753761/

2017: A review of CBD & Alzheimer's disease

In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer's Disease

https://pubmed.ncbi.nlm.nih.gov/28217094/

2017: CBD & Alzheimer's disease

The therapeutic potential of the phytocannabinoid cannabidiol for Alzheimer's disease

https://pubmed.ncbi.nlm.nih.gov/27471947/

2015: The ECS & the neurodegeneration of Alzheimer's disease

The role of endocannabinoid signaling in the molecular mechanisms of neurodegeneration in Alzheimer's disease

https://pubmed.ncbi.nlm.nih.gov/25147120/

Chart Gallery

CBD in AD & epilepsy
CBD in AD & epilepsy

2020: Overview of cannabidiol (CBD) and its analogues: Structures, biological activities, and neuroprotective mechanisms in epilepsy and Alzheimer's disease

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Neuroprotection of cannabinoids in AD
Neuroprotection of cannabinoids in AD

2020: Emerging Promise of Cannabinoids for the Management of Pain and Associated Neuropathological Alterations in Alzheimer's Disease

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CB2 in AD
CB2 in AD

2016: CB2 Cannabinoid Receptor As Potential Target against Alzheimer's Disease

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CBD in AD & epilepsy
CBD in AD & epilepsy

2020: Overview of cannabidiol (CBD) and its analogues: Structures, biological activities, and neuroprotective mechanisms in epilepsy and Alzheimer's disease

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Timeline of Research

2021: In a mouse model of Alzheimer’s disease, an analog of anandamide protected the brain via regulation of autophagy (the recycling system of the brain) via the CB1 & CB2 receptor

N-linoleyltyrosine exerts neuroprotective effects in APP/PS1 transgenic mice via cannabinoid receptor-mediated autophagy

https://www.sciencedirect.com/science/article/pii/S1347861321000839

2021: In a rat model of Alzheimer’s disease, activation of the CB1 receptor lessened cognitive impairment by lowering oxidative stress & enhancing neurogenesis (the creation of new brain cells)

WIN55,212-2 Attenuates Cognitive Impairments in AlCl3 + d-Galactose-Induced Alzheimer’s Disease Rats by Enhancing Neurogenesis and Reversing Oxidative Stress

https://www.mdpi.com/2227-9059/9/9/1270

2021: In rats fed a high-fat diet, CBD reduced insulin resistance & decreased the tau protein associated with Alzheimer’s disease

Cannabidiol - A phytocannabinoid that widely affects sphingolipid metabolism under conditions of brain insulin resistance

https://pubmed.ncbi.nlm.nih.gov/34435590/

2021: In neurons of the hippocampus, activating the CB2 receptor protected them from the Aβ plaques associated with Alzheimer’s

Effects of CB2 Receptor Agonist JWH133 on Aβ42-Induced Hippocampal Neurons

https://www.ijsciences.com/pub/article/2353

2021: In a mouse model of Alzheimer’s, inhibiting the FAAH enzyme lowers inflammation of the microglia (brain immune cells) via several different cellular processes

Fatty Acid Amide Hydrolase (FAAH) Inhibition Modulates Amyloid-Beta-Induced Microglia Polarization

https://pubmed.ncbi.nlm.nih.gov/34299330/

2020: In mouse model of AD, CBD helped “on social recognition memory and spatial learning deficits” and Aβ40 plaque levels

Chronic Treatment with 50 mg/kg Cannabidiol Improves Cognition and Moderately Reduces Aβ40 Levels in 12-Month-Old Male AβPPswe/PS1ΔE9 Transgenic Mice

https://pubmed.ncbi.nlm.nih.gov/32116258/

2020: In a mouse model of AD, CBD helped by enhancing the immune system response & the pathway for autophagy (regulated cell recycling & digestion of damaged or unnecessary cellular components)

Cannabidiol (CBD) enhanced the hippocampal immune response and autophagy of APP/PS1 Alzheimer's mice uncovered by RNA-seq

https://pubmed.ncbi.nlm.nih.gov/33096116/

2020: In rat brain cells, activating CB2 receptors protects from the damage of beta-amyloid peptides of Alzheimer’s

Activation of cannabinoid receptor 2 protects rat hippocampal neurons against Aβ-induced neuronal toxicity

https://pubmed.ncbi.nlm.nih.gov/32592731/

2020: In a cellular model of Alzheimer’s, the endocannabinoid PEA protects the neurons & increases their survival

Astrocytic palmitoylethanolamide pre-exposure exerts neuroprotective effects in astrocyte-neuron co-cultures from a triple transgenic mouse model of Alzheimer's disease

https://pubmed.ncbi.nlm.nih.gov/32622942/

2020: In a patient with advanced Alzheimer's, low levels of THC (dronabinol) allowed her to drop 3 out of her 6 medications while improving emotional state and lessening aggression

Cannabinoid as Beneficial Replacement Therapy for Psychotropics to Treat Neuropsychiatric Symptoms in Severe Alzheimer's Dementia: A Clinical Case Report

https://pubmed.ncbi.nlm.nih.gov/32477187/

2020: In tissue samples from patients with Alzheimer's and in mouse models, increased MAGL (which breaks down 2-AG) could be a biomarker to suggest the use of the diabetic drug metformin to help with neurogenesis and spatial memory

Dysregulated expression of monoacylglycerol lipase is a marker for anti-diabetic drug metformin-targeted therapy to correct impaired neurogenesis and spatial memory in Alzheimer's disease

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255032/

2020: In mice with AD, CBD improved cognition and decreased anxiety

Cannabidiol (CBD) Improves Cognition and Decreases Anxiety in the SAMP8 Mouse Model of Alzheimer’s

https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.2020.34.s1.09741

2020: In mice with AD, treatment with THC reduced their plaques & restored memory function

Prolonged Tetrahydrocannabinol treatment reduces amyloid plaque deposition and restores memory function in the 5XFAD mouse model of Alzheimer’s disease

https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0040-1708321

2019: In humans with Alzheimer’s, nabilone (THC) improved agitation (39 patients in randomized double-blind crossover trial)

Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer's Disease

https://www.ncbi.nlm.nih.gov/pubmed/31182351

2019: In mouse brain slices simulating AD, CBD protected the hippocampus – perhaps by PPARα

Cannabidiol Reverses Deficits in Hippocampal LTP in a Model of Alzheimer's Disease

https://www.ncbi.nlm.nih.gov/pubmed/29574668

2019: In humans, a pilot study in Geneva shows CBD/THC combo helps dementia patients (10 patients in a prospective observational study)

A pilot study in Geneva shows CBD/THC combo helps dementia patients

https://www.karger.com/Article/Abstract/498924

“Half of the patients decreased or stopped other psychotropic medications. The staff appreciated the decrease in rigidity, making daily care and transfers easier, the improved direct contact with the patients, the improvement in behavior, and the decrease in constipation with less opioids. There was no withholding of the medication for reasons of side effects, and the effects persisted after 2 months. Conclusions: An oral cannabis extract with THC/CBD, in higher dosages than in other studies, was well tolerated and greatly improved behavior problems, rigidity, and daily care in severely demented patients.”

2017: In humans with dementia, low levels of THC seem to be safe for balance and gait

Effects of tetrahydrocannabinol on balance and gait in patients with dementia: A randomised controlled crossover trial

https://www.ncbi.nlm.nih.gov/pubmed/27624148

2018: In microglial cells, CB1/CB2 heterocomplexes could be a target for AD

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

https://www.ncbi.nlm.nih.gov/pubmed/28843453

2017: In cells, CBD lessens oxidative stress, mitochondrial dysfunction and reactive oxygen species generation via Wnt/β-catenin pathway and PPARγ

Effects of cannabidiol interactions with Wnt/β-catenin pathway and PPARγ on oxidative stress and neuroinflammation in Alzheimer's disease

https://www.ncbi.nlm.nih.gov/pubmed/28981597

2016: In stem cells, CBD modulates the expressions of genes related to Alzheimer’s

Cannabidiol Modulates the Expression of Alzheimer’s Disease-Related Genes in Mesenchymal Stem Cells

https://www.ncbi.nlm.nih.gov/pubmed/28025562

2015: In humans with dementia, low levels of THC were safe but did not reduce symptoms

Tetrahydrocannabinol in Behavioral Disturbances in Dementia: A Crossover Randomized Controlled Trial

https://www.ncbi.nlm.nih.gov/pubmed/26560511

2015: In humans with dementia, low doses of THC is safe but not effective for neuropsychiatric symptoms

Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: A randomized controlled trial

https://www.ncbi.nlm.nih.gov/pubmed/25972490

2015: In a mouse model of AD, JZL184 (MGL inhibitor) lessens neuroinflammation

Monoacylglycerol lipase inhibitor JZL184 reduces neuroinflammatory response in APdE9 mice and in adult mouse glial cells

http://www.ncbi.nlm.nih.gov/pubmed/25927213

2015: In a mouse model of AD, THC + CBD reduced learning impairment, astrogliosis, microgliosis, and inflammatory-related molecules

Cannabis-based medicine reduces multiple pathological processes in AβPP/PS1 mice

http://www.ncbi.nlm.nih.gov/pubmed/25125475

2014: In a mouse model of AD, the CB1 expression is altered, suggesting a therapeutic target

Altered expression of the CB1 cannabinoid receptor in the triple transgenic mouse model of Alzheimer's disease

http://www.ncbi.nlm.nih.gov/pubmed/24496074

2014: In a cellular model of AD, THC lowers amyloid beta proteins - directly interacts with peptide - lowers GSK - enhances mitochondria function

The potential therapeutic effects of THC on Alzheimer's disease

http://www.ncbi.nlm.nih.gov/pubmed/25024327

2014: In a mouse model of AD, CBD protected from onset and helped for symptoms of social withdrawal and facial recognition

Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer's disease transgenic mice

https://pubmed.ncbi.nlm.nih.gov/25024347/

2014: In humans with AD, postmortem brain samples showed altered CB1 expression

Type-1 cannabinoid receptor activity during Alzheimer's disease progression

http://www.ncbi.nlm.nih.gov/pubmed/24946872

2014: In brain slices, B-amyloid suppresses CB1

β-Amyloid inhibits E-S potentiation through suppression of cannabinoid receptor 1-dependent synaptic disinhibition

https://pubmed.ncbi.nlm.nih.gov/24945775/

2014: In rats model of AD, cognition & memory improved by CBD

Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1∆E9 mice

http://www.ncbi.nlm.nih.gov/pubmed/24577515

2014: In cells, CBD increases neuronal survival in model of AD by reducing apoptosis and decreasing amyloid precursor protein levels via PPARγ receptor

Cannabidiol promotes amyloid precursor protein ubiquitination and reduction of beta amyloid expression in SHSY5YAPP+ cells through PPARγ involvement

https://www.ncbi.nlm.nih.gov/pubmed/24288245

2013: In a mouse model of tauopathy, phytocannabinoids improve dopamine transmission and the pathology of tau and amyloid plaques

Natural cannabinoids improve dopamine neurotransmission and tau and amyloid pathology in a mouse model of tauopathy

http://www.ncbi.nlm.nih.gov/pubmed/23478312

2013: In an animal model of AD, ECS helped to clear the beta-amyloid’s across the blood-brain barrier

Role of the cannabinoid system in the transit of beta-amyloid across the blood-brain barrier

https://pubmed.ncbi.nlm.nih.gov/23831388/

2013: In mice, activating CB2 helps with AD

CB2 cannabinoid receptor agonist ameliorates Alzheimer-like phenotype in AβPP/PS1 mice

https://www.ncbi.nlm.nih.gov/pubmed/23515018/

2011: In the postmortem brains of Alzheimer’s patients, a look at the state of the ECS

Molecular reorganization of endocannabinoid signalling in Alzheimer's disease

https://pubmed.ncbi.nlm.nih.gov/21459826/

2011: In a mouse model of AD, CBD lessens the activation of the microglia

Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo: relevance to Alzheimer's disease

https://www.ncbi.nlm.nih.gov/pubmed/21350020

2011: In a rat model of AD, CBD’s help may be mediated by the PPARγ nuclear receptor – reduces damage from reactive oxygen species

Cannabidiol reduces Aβ-induced neuroinflammation and promotes hippocampal neurogenesis through PPARγ involvement

https://www.ncbi.nlm.nih.gov/pubmed/22163051/

2008: In humans with dementia, nabilone helps with agitation

The cannabinoid receptor agonist nabilone for the treatment of dementia-related agitation

https://www.ncbi.nlm.nih.gov/pubmed/18081000

2007: In a mouse model of AD, CBD helps via several pathways

Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression

https://www.ncbi.nlm.nih.gov/pubmed/17592514/

2006: In cells, CBD prevents beta-amyloid induced neuronal death via its ability to scavenge reactive oxygen species

Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in beta-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-kappaB involvement

https://www.ncbi.nlm.nih.gov/pubmed/16490313

2006: In humans with severe dementia, THC helped for agitation at night (6 patients in an open-label pilot study)

Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia

https://www.ncbi.nlm.nih.gov/pubmed/16521031

2006: In cell cultures, CBD helps in AD because it “inhibits hyperphosphorylation of tau protein”

The marijuana component cannabidiol inhibits beta-amyloid-induced tau protein hyperphosphorylation through Wnt/beta-catenin pathway rescue in PC12 cells

https://www.ncbi.nlm.nih.gov/pubmed/16389547

2006: In cell cultures, CBD inhibits damage of beta-amyloids

CB1 receptor selective activation inhibits beta-amyloid-induced iNOS protein expression in C6 cells and subsequently blunts tau protein hyperphosphorylation in co-cultured neurons

https://www.ncbi.nlm.nih.gov/pubmed/16837132/

2006: In rodents, after insult with a beta-amyloid, 2-AG levels rise

Endocannabinoids and beta-amyloid-induced neurotoxicity in vivo: effect of pharmacological elevation of endocannabinoid levels

https://www.ncbi.nlm.nih.gov/pubmed/16732431/

2006: In a tissue model of AD, compared to other drugs, ‘THC is a considerably superior inhibitor of Aβ aggregation’

A Molecular Link Between the Active Component of Marijuana and Alzheimer's Disease Pathology

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562334/

2005: In the brains of humans & in rats, cannabinoids protect by blocking microglial activation in senile plaques

Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation

https://www.ncbi.nlm.nih.gov/pubmed/15728830/

2004: In a model of AD cells, pretreatment with CBD reduced reactive oxygen species (free radicals) and other protective effects

Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells

https://www.ncbi.nlm.nih.gov/pubmed/15030397

2003: In a mouse model of AD, injecting beta-amyloid fragments into the brain causes amnesia – but this can be attenuated by blocking CB1 receptor

Amnesia induced by beta-amyloid fragments is counteracted by cannabinoid CB1 receptor blockade

https://www.ncbi.nlm.nih.gov/pubmed/14522360

2003: In brains of deceased AD patients, CB2 and FAAH overexpressed – CB1 unchanged

Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer's disease brains

https://www.ncbi.nlm.nih.gov/pubmed/14657172

1997: In humans with AD, dronabinol helped with anorexia & disturbance (15 patients in a placebo-controlled crossover design)

Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease

https://www.ncbi.nlm.nih.gov/pubmed/9309469