Dementia & Alzheimer's Disease
Best reviews
2022: A review on using the cannabinoids to treat Alzheimer’s
Impact of the cannabinoid system in Alzheimer's diseases
https://pubmed.ncbi.nlm.nih.gov/35105293/
2022: A review on the metabolism of endocannabinoids & their relation to Alzheimer’s disease
Endocannabinoid metabolism and Alzheimer’s disease
2022: This review of Alzheimer’s suggests increasing the antioxidant & endocannabinoid levels
Simultaneous Elevation Of Antioxidant And Endocannabinoid Defense System May Prevent Dementia And Improve Cognitive Function In Humans
2022: This review covers the role of FAAH inhibitors (which include CBD) for treating Alzheimer’s disease
The role of fatty acid amide hydrolase enzyme inhibitors in Alzheimer's disease
https://pubmed.ncbi.nlm.nih.gov/34931308/
2021: This review of circadian rhythm dysfunction in Alzheimer’s disease suggests endocannabinoids as a target for decelerating the progress of the disease
Orchestration of the circadian clock and its association with Alzheimer's disease: role of endocannabinoid signaling
https://pubmed.ncbi.nlm.nih.gov/34844016/
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
2020: Overview of cannabidiol (CBD) and its analogues: Structures, biological activities, and neuroprotective mechanisms in epilepsy and Alzheimer's disease
2020: Emerging Promise of Cannabinoids for the Management of Pain and Associated Neuropathological Alterations in Alzheimer's Disease
2016: CB2 Cannabinoid Receptor As Potential Target against Alzheimer's Disease
2020: Overview of cannabidiol (CBD) and its analogues: Structures, biological activities, and neuroprotective mechanisms in epilepsy and Alzheimer's disease
Timeline of Research
2022: In a mouse model of dementia, CBD helped to maintain their spatial memory, reduce their anxiety & lessen fear-associated freezing
Cannabidiol (CBD) treatment improves spatial memory in 14-month-old female TAU58/2 transgenic mice
https://pubmed.ncbi.nlm.nih.gov/35202719/
2022: In a tissue model of Alzheimer’s disease, some cannabis terpenes provided neuroprotection against the toxic neurofibrillary tangles
Cannabis terpenes display variable protective and anti-aggregatory actions against neurotoxic β amyloid in vitro: highlighting the protective bioactivity of α-bisabolol in motorneuronal-like NSC-34 cells
https://pubmed.ncbi.nlm.nih.gov/35278524/
2022: In a mouse model of Alzheimer’s disease, low doses of THC decreased biomarkers of the disease
Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APP/PS1 Mice
https://www.mdpi.com/1422-0067/23/5/2757/htm
2022: In a worm model of Alzheimer’s, CBD prevented disease progression via the scavenging of reactive oxygen species
Cannabidiol protects against Alzheimer's disease in C. elegans via ROS scavenging activity of its phenolic hydroxyl groups
https://pubmed.ncbi.nlm.nih.gov/35181336/
2022: In a tissue model of Alzheimer’s disease, CBD lowered the aggregation of the tau proteins
Cannabidiol Inhibits Tau Aggregation In Vitro
https://pubmed.ncbi.nlm.nih.gov/34944028/
2021: In humans, the endocannabinoid levels in the blood might be useful biomarkers for dementia & Alzheimer’s patients
Alterations of plasma endocannabinoid levels in MCI and dementia patients
2021: In a mouse model of Alzheimer’s disease, CBD coated by nano-particles reduced brain plaques, increased CB1 & CB2 levels & improved learning & memory
The Effect of Cannabidiol Coated by Nano-Chitosan on Learning and Memory, Hippocampal CB1 and CB2 Levels, and Amyloid Plaques in an Alzheimer's Disease Rat Model
https://pubmed.ncbi.nlm.nih.gov/34727550/
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