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. According to the World Alzheimer 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 case are diagnosed as Alzheimer’s disease (AD) making it the leading form of dementia.


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, behavioral problems including agitation, mood disturbances and psychosis. AD is often characterized by the presence of neurofibrillary tangles (NFTs) and neuritic plaques (2).

Alzheimer disease brain slice
Photograph of a slice of AD brain magnified 100x. Numerous senile (neuritic) plaques (black arrows) and neurofibrillary tangles (red arrow) are shown. Source: Mt Sinai J Med. 2010 Jan-Feb; 77(1): 32–42.

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). 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 diarrhea, nausea, vomiting, insomnia, fatigue and dizziness. Other drug therapies for AD include nicotine, melatonin, estrogens (8) and an N-methyl-D-aspartate receptor antagonist named memantine (9). However, the current AD drug therapy is ineffective and only provides a short-term delay progression of AD. Moreover, although there was a close association of the use of non-steroidal antiinflammatory drugs (NSAIDs) and a lower incidence of AD, patients suffered from withdrawal syndrome as a result of gastrointestinal toxicity (9).



Targets od cannabinoid activity
Some of the targets of cannabinoids in AD patients. Source: Neurochem Res (2012) 37:1829–1842.


CBD has many modes of action that have been found to be beneficial in AD. This cannabinoid has been shown to have neuroprotective properties against Aβ peptide (10,11), preventing memory deficits (12) and inhibiting 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 resulted in the reduction of neuronal apoptosis (13). Additionally, also presents anti-inflammatory, neuroprotective and anti-oxidant effects (12,13,14,15).


THC promoted the survival of neuronal cultures exposed to Aβ peptide (11,16) and by significantly increased the expression of neprilysin leading to a remarkable reduction of Aβ plaques (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 protective, removed intraneuronal Aβ and completely eliminated the 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 mitochondrial activity (20).



There have been very few clinical trials done on this subject and 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).

We have seen 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 months 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 had to communicate with and was in his own world had similar results. After a month of microdosing wholeplant extract therapy (high THC acidic 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 that we witnessed first had, 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 a sense of normality.


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 antinflamatory 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 (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.



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