Alzheimer’s Disease & Cannabis
Dementia: a Global Epidemic
We often hear of dementia as a debilitating worldwide problem of our ageing population.
Dementia actually isn’t a specific disease but it describes a group of symptoms affecting memory, thinking and social abilities severely enough to interfere with daily functioning.
We recommend to use these simple tools to boost your mental capabilities with yoga as described in this article and to nourish your brain properly with these memory-boosting foods (“How to prevent and slow the progression of Alzheimer’s disease with a correct nutrition”)
According to the World Alzheimer’s Disease Report of 2015 (1), it was estimated that 46.8 million people worldwide were living with dementia (Asia 22.9, Europe 10.5, The Americas 9.4 and Africa 4 million people).
This number will almost double every 20 years, reaching 74.7 million in 2030 and 131.5 million in 2050.
The regional distribution of new dementia cases in 2015 was 4.9 million (49% of the total) in Asia, 2.5 million (25%) in Europe, 1.7 million (18%) in the Americas, and 0.8 million (8%) in Africa.
More than half of these cases are diagnosed as Alzheimer’s disease (AD) making it the leading form of dementia.
Alzheimer’s Disease: an insight
Alzheimer’s disease (AD) is a progressive neuro-degenerative disorder associated with memory impairment and cognitive deficit.
Other features associated with the later stages of AD include language deficits, depression, behavioural problems including agitation, mood disturbances and psychosis.
AD is often characterized by the presence of neurofibrillary tangles (NFTs) and neuritic plaques (2).
Neuritic or senile plaques are complex extracellular lesions composed of a core of β-amyloid (Aβ) aggregates due to accumulation of non-soluble fragments of amyloid precursor protein (APP). β-amyloid form these plaques in predominantly limbic regions of the brain which leads to local inflammatory responses and neurodegeneration in brain areas relevant for memory processing (i.e., amygdala, hippocampus and frontal cortex).
The second hallmark of AD is the hyperphosphorylation of the cytoskeletal microtubule-associated protein tau (3). Tau phosphorylation promotes its aggregation leading to the formation of intracellular neurofibrillary tangles (NFT), thereby impairing intra-neuronal communication.
A major neurochemical deficit in AD brains is also decrease in acetylcholine (ACh), a neurotransmitter which plays a role in cortical development and activity and the modulation of cognition, learning and memory (4). We addressed this issue, and how to boost ACh naturally with the right foods here.
Other consequences of AD in the brain are overly activated microglia cells and altered mitochondrial functioning (5) that lead to oxidative stress and production of pro-inflammatory cytokines and chemokines that cause neuroinflammation and neurotoxicity.
AChE inhibitor treatment has been shown to improve the cognitive performance as well as activities of daily living but only in patients with mild to moderate forms of AD (6) and only short-term (from 9-12 months to 5 years).
Donepezil and Galantamine have also been documented to inhibit NO-induced cytotoxicity (via production of radicals and mitochondrial dysfunction) and counteract neuronal cell death (7), which may have contributed to their initial treatment success. Potential side effects include diarrhoea, nausea, vomiting, insomnia, fatigue and dizziness.
We have examined in another article “How to decrease the side effects of Alzheimer’s Disease medication with diet”.
Other drug therapies for AD include nicotine, melatonin, oestrogens (8) and an N-methyl-D-aspartate receptor antagonist named Memantine. (9)
Moreover, although there was a close association of the use of non-steroidal anti-inflammatory drugs (NSAIDs) and a lower incidence of AD, patients suffered from withdrawal syndrome as a result of gastrointestinal toxicity, so also this therapeutic option has given little promise. (9)
Unfortunately current AD drug therapy is ineffective and only provides a short-term delay progression of AD.
Alzheimer’s Disease & Cannabis: how do cannabinoids help with AD?
This cannabinoid has been shown to have neuroprotective properties against Aβ peptide (10,11), preventing memory deficits (12).
Moreover, CBD inhibits tau protein hyper-phosphorylation through the reduction of the phosphorylated active form of glycogen synthase kinase 3β (GSK-3β), one of the known tau kinases, which results in the reduction of neuronal apoptosis (neuronal death) (13).
Additionally, the well known anti-inflammatory, neuroprotective and anti-oxidant effects of CBD are proving to be key in preventing further degeneration. (12,13,14,15).
In experiments carried out in-vitro, THC promoted the survival of neuronal cultures exposed to Aβ peptide (11,16). Aβ plaques have been found remarkably reduced when exposed to THC, which acted by significantly increasing the expression of neprilysin, an enzyme which degrades Aβ peptide (17).
Δ9-THC also competitively inhibits AChE, thus increasing ACh levels, as well as preventing AChE-induced Aβ aggregation (18).
A study published in 2016 which was done on human neuronal cells showed that from all the compounds tested (endocannabinoids, synthetic cannabinoids, other compounds), THC was the most potent CB-1 agonist (EC50 below 50 nmol/l) and that it was neuroprotective.
It removed intraneuronal Aβ accumulations and completely eliminated the harmful elevated eicosanoid production.
This study showed that cannabinoids are able to prevent the accumulation of intraneuronal Aβ, reduce the production of eicosanoids and block nerve cell death (19).
Studies done with Sativex, a 1:1 mixture of Δ9-THC and CBD, have shown marked reductions in neurofibrillary tangles, microglial activity, free radicals and damaged mitochondrial activity, which further confirmed the potential of cannabinoids in treating Alzheimer’s Disease. (20)
There have been very few clinical trials done on this subject; The ones that were done used synthetic cannabinoids and not whole plant extracts. A recent open label pilot study with 10 patients reported significant decrease in factors such as delusions, agitation/aggression, irritability, apathy, sleep and caregiver distress (21).
However, there is countless anecdotal evidence which shows very promising and nearly miraculous recoveries in various AD patients.
In the case of an elderly gentleman, who did not communicate with people and who was, as described by his family, “in his own world”, the changes after only one and a half month of microdosing cannabis wholeplant extract therapy (2:3 THC:CBD ratio) were astonishing. He started communicating normally with family members, he felt much better and, much to his whole family’s surprise, he started to play the accordion again.
Another case of a 70-year-old gentleman who also was hard to communicate with, and was in apathetic state, had similar results. After a month of microdosing wholeplant extract therapy (high THCA and neutral cannabinoids), besides his improvement in sleep and overall wellbeing, he started talking more comprehensively and after 3 months of therapy his wife could not stop him from talking.
These are just 2 cases among many others that have shown the healing potential of cannabis extracts, not only in alleviating the symptoms and stopping the disease from progressing, but also in reversing many lost abilities and giving patients and their families a sense of normality.
If you are currently caring for someone with AD, we wrote something for you here.
With an ever growing elderly population, neurodegenerative diseases are on the rise and conventional medicine does not have a true solution for this major problem.
Cannabinoids, with their neuroprotective, antioxidant and antinflammatory properties, have been shown to have a myriad of effects on the symptoms, halting and reversing of this debilitating disease.
Research in this area has given us a better understanding of the mechanism of action of cannabinoids on the major issues involving AD.
It is safe to say that treating AD with whole plant cannabinoid preparations is an effective strategy along with a proper diet and use of neuroprotective functional foods, discover which ones here. (22,23,24).
As research has demonstrated, even very small doses have a positive effect, so preventive cannabinoid therapy with microdosing should be considered for people over a certain age or prone to this kind of degenerative diseases.
Did you like this article?
This original content has been offered for free without advertisements thanks to our readers’ contributions. You, too, can support us in many ways. Check out how here! Thank you
Copyright, Nature Going Smart. May not be re-printed without permission.
World Alzheimer Report 2015 – The Global Impact of Dementia. An analysis of prevalence, incidence, cost & trends. 2015. Alzheimer’s Disease International.
Hardy, J., Selkoe, D.J., 2002. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297, 353–356.
Kidd M. Paired helical filaments in electron microscopy of Alzheimer’s disease. Nature 1963;197:192-3.
Hasselmo M. E. 2006. The Role of Acetylcholine in Learning and Memory. Curr Opin Neurobiol. 2006 Dec; 16(6): 710–715.
Mattson MP. Pathways towards and away from Alzheimer’s disease. Nature 2004;430:631-9.
Mancuso C, Siciliano R, Barone E, et al. Pharmacologists and Alzheimer disease therapy: to boldly go where no scientist has gone before. Expert Opin Investig Drugs 2011;20:1243-61.
Takada-Takatori Y, Kume T, Izumi Y, et al. Roles of nicotinic receptors in acetylcholinesterase inhibitor-induced neuroprotection and nicotinic receptor up-regulation. Biol Pharm Bull 2009;32:318-24
Coˆte´ S, Carmichael PH, Verreault R, et al. (2012). Nonsteroidal antiinflammatory drug use and the risk of cognitive impairment and Alzheimer’s disease. Alzheimers Dement, 8, 219–26.
Hong-Qi Y, Zhi-Kun S, Sheng-Di C. (2012). Current advances in the treatment of Alzheimer’s disease: focused on considerations targeting Ab and tau. Transl Neurodegener, 1, 21.
Iuvone, T., Esposito, G., Esposito, R., Santamaria, R., Di Rosa, M., and Izzo, A. A. (2004). Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells. J. Neurochem. 89, 134–141.
Janefjord, E., Mååg, J. L., Harvey, B. S., and Smid, S. D. (2013). Cannabinoid effects on β amyloid fibril and aggregate formation, neuronal and microglial-activated neurotoxicity in vitro. Cell. Mol. Neurobiol. 34, 31–42.
Martín-Moreno, A. M., Reigada, D., Ramírez, B. G., Mechoulam, R., Innamorato, N., Cuadrado, A., et al. (2011). Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo: relevance to Alzheimer’s disease.Mol. Pharmacol. 79, 964–973.
Esposito, G., De Filippis, D., Carnuccio, R., Izzo, A. A., and Iuvone, T. (2006a). The marijuana component cannabidiol inhibits beta-amyloid-induced tau protein hyperphosphorylation through Wnt/beta-catenin pathway rescue in PC12 cells.J. Mol. Med. 84, 253–258.
Esposito, G., De Filippis, D., Steardo, L., Scuderi, C., Savani, C., Cuomo, V., et al. (2006b). CB1 receptor selective activation inhibits beta-amyloid-induced iNOS protein expression in C6 cells and subsequently blunts tau protein hyperphosphorylation in co-cultured neurons. Neurosci. Lett. 404, 342–346.
Esposito, G., Scuderi, C., Valenza, M., Togna, G. I., Latina, V., De Filippis, D., et al. (2011). Cannabidiol reduces Aβ-induced neuroinflammation and promotes hippocampal neurogenesis through PPARγ involvement. PLoS ONE 6:e28668.
Ramírez, B. G., Blázquez, C., Gómez del Pulgar, T., Guzmán M., and de Ceballos, M. L. (2005). Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J. Neurosci. 25, 1904–1913.
Chen, R., Zhang. J., Fan, N., Teng, Z. Q., Wu, Y., Yang, H., et al. (2013). Δ(9)-THC-caused synaptic and memory impairments are mediated through COX-2 signaling. Cell 155, 1154–1165.
Eubanks, L. M., Rogers, C. J., Beuscher, A. E. IV, Koob, G. F., Olson, A. J., Dickerson, T. J., et al. (2006). A molecular link between the active component of marijuana and Alzheimer’s disease pathology. Mol. Pharm. 3, 773–777.
Currais A, Oswald Quehenberger, Aaron M Armando, Daniel Daugherty, Pam Maher, David Schubert. Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids. npj Aging and Mechanisms of Disease, 2016; 2: 16012.
Casarejos, M. J., Perucho, J., Gómez, A., Muñoz, M. P., Fernández-Estévez, M., Sagredo, O., et al. (2013). Natural cannabinoids improve dopamine neurotransmission and tau and amyloid pathology in a mouse model of tauopathy. J. Alzheimers Dis. 35, 525–539.
Shelef A, Barak Y, Berger U, Paleacu D, Tadger S, Plopsky I, Baruch Y. 2016. Safety and Efficacy of Medical Cannabis Oil for Behavioral and Psychological Symptoms of Dementia: An-Open Label, Add-On, Pilot Study. J Alzheimers Dis. 2016;51(1):15-9.
Essa MM, Vijayan RK, Castellano-Gonzalez G, et al. 2012. Neuroprotective effect of natural products against Alzheimer’s disease. Neurochem Res, 37, 1829–42
Parvathy R. Kumar, Musthafa Mohamed Essa, Samir Al-Adawi, Ghazi Dradekh,Mushtaq A. Memon, Mohammed Akbar, Thamilarasan Manivasagam. 2014. Omega-3 Fatty Acids Could Alleviate the Risks of Traumatic Brain Injury – A Mini Review. J Tradit Complement Med. 2014 Apr-Jun; 4(2): 89–92.
Selvaraju Subash, Musthafa Mohamed Essa, Samir Al-Adawi, Mushtaq A. Memon, Thamilarasan Manivasagam, Mohammed Akbar. 2014. Neuroprotective effects of berry fruits on neurodegenerative diseases. Neural Regen Res. 2014 Aug 15; 9(16): 1557–1566.