https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481530Ageing is associated with a decline of motor coordination [1], sensory abilities [2], attention and cognitive performance [3], which together are responsible for the increasing deficits in learning and memory tasks. However, as with all age-related health issues, there is a wide spectrum of potential outcomes: While many senior citizens still enjoy their cognitive abilities at an advanced age, others, especially those who suffer from neurodegenerative disorders such as Alzheimer's disease (AD), may show signs of cognitive impairment early in their life. Thus, a better understanding of the molecular and cellular processes that contribute to, or protect against, cognitive decline, may offer novel routes for therapy and prevention.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942876:    Considering the numerous complex pathological mechanisms involved in the progression of AD, treatments targeting a single causal or modifying factor offer limited benefit. Cannabinoids, however, exhibit pleiotropic activity, targeting in parallel several processes that play key roles in AD, including Aβ and tau aberrant processing, neuroinflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress. Cannabinoids improve behavioral disturbances, as well. These effects are summarized in Figure ​Figure11. Then, because of these widespread properties of cannabinoid compounds, targeting the ECS could represent a unique and reliable opportunity to advance toward an effective therapy against the AD. Moreover, cannabinoids might represent a safe low-cost therapy, with their natural origin and low side effects profile. From our point of view, the success of cannabinoid-based therapy in AD could be increased taking into account two important aspects: (i) the use of a combination of compounds that cover the whole spectrum of therapeutic properties described for cannabinoids, i.e., combination of CB1 and CB2 receptors agonists plus CBD, which presents interesting neuroprotective properties spite of its mechanism of action remaining poorly understood, and (ii) the early initiation of the treatment in the neurodegenerative process, which ensures the integrity of the ECS target components and increases the possibility of curbing the exponential degenerative progression toward dementia.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931550The unifying hypothesis encompassing most of these studies is that pathologic changes in endocannabinoid levels and CB2 expression are induced by the inflammatory environment which occurs in AD. Activation of CB2 by up-regulated endocannabinoids goes some way towards halting microglial activation; however, this innate compensation is insufficient to prevent the subsequent inflammatory damage to neurons, which may also suffer from a loss of protection due to the down-regulation of CB1. On the basis of the pre-clinical efficacy already demonstrated, cannabinoid stimulators may have therapeutic benefit by augmenting the brain's innate response.


http://www.ncbi.nlm.nih.gov/pubmed/25024327The purpose of this study was to investigate the potential therapeutic qualities of Δ9-tetrahydrocannabinol (THC) with respect to slowing or halting the hallmark characteristics of Alzheimer's disease. N2a-variant amyloid-β protein precursor (AβPP) cells were incubated with THC and assayed for amyloid-β (Aβ) levels at the 6-, 24-, and 48-hour time marks. THC was also tested for synergy with caffeine, in respect to the reduction of the Aβ level in N2a/AβPPswe cells. THC was also tested to determine if multiple treatments were beneficial. The MTT assay was performed to test the toxicity of THC. Thioflavin T assays and western blots were performed to test the direct anti-Aβ aggregation significance of THC. Lastly, THC was tested to determine its effects on glycogen synthase kinase-3β (GSK-3β) and related signaling pathways. From the results, we have discovered THC to be effective at lowering Aβ levels in N2a/AβPPswe cells at extremely low concentrations in a dose-dependent manner. However, no additive effect was found by combining caffeine and THC together. We did discover that THC directly interacts with Aβ peptide, thereby inhibiting aggregation. Furthermore, THC was effective at lowering both total GSK-3β levels and phosphorylated GSK-3β in a dose-dependent manner at low concentrations. At the treatment concentrations, no toxicity was observed and the CB1 receptor was not significantly upregulated. Additionally, low doses of THC can enhance mitochondria function and does not inhibit melatonin's enhancement of mitochondria function. These sets of data strongly suggest that THC could be a potential therapeutic treatment option for Alzheimer's disease through multiple functions and pathways.



http://www.ncbi.nlm.nih.gov/pubmed/26757043
  Tetrahydrocannabinol (THC) is a potential treatment for Alzheimer's disease (AD).  Objective: To measure efficacy and safety of medical cannabis oil (MCO) containing THC as an add-on to pharmacotherapy, in relieving behavioral and psychological symptoms of dementia (BPSD).


Eleven AD patients were recruited to an open label, 4 weeks, prospective trial.  Ten patients completed the trial. Significant reduction in CGI severity score (6.5 to 5.7; p < 0.01) and NPI score were recorded (44.4 to 12.8; p < 0.01). NPI domains of significant decrease were: Delusions, agitation/aggression, irritability, apathy, sleep and caregiver distress.  Adding MCO to AD patients' pharmacotherapy is safe and a promising treatment option.


http://www.ncbi.nlm.nih.gov/pubmed/25024327 The purpose of this study was to investigate the potential therapeutic qualities of Δ9-tetrahydrocannabinol (THC) with respect to slowing or halting the hallmark characteristics of Alzheimer's disease. N2a-variant amyloid-β protein precursor (AβPP) cells were incubated with THC and assayed for amyloid-β (Aβ) levels at the 6-, 24-, and 48-hour time marks. THC was also tested for synergy with caffeine, in respect to the reduction of the Aβ level in N2a/AβPPswe cells. THC was also tested to determine if multiple treatments were beneficial. The MTT assay was performed to test the toxicity of THC. Thioflavin T assays and western blots were performed to test the direct anti-Aβ aggregation significance of THC. Lastly, THC was tested to determine its effects on glycogen synthase kinase-3β (GSK-3β) and related signaling pathways. From the results, we have discovered THC to be effective at lowering Aβ levels in N2a/AβPPswe cells at extremely low concentrations in a dose-dependent manner. However, no additive effect was found by combining caffeine and THC together. We did discover that THC directly interacts with Aβ peptide, thereby inhibiting aggregation. Furthermore, THC was effective at lowering both total GSK-3β levels and phosphorylated GSK-3β in a dose-dependent manner at low concentrations. At the treatment concentrations, no toxicity was observed and the CB1 receptor was not significantly upregulated. Additionally, low doses of THC can enhance mitochondria function and does not inhibit melatonin's enhancement of mitochondria function. These sets of data strongly suggest that THC could be a potential therapeutic treatment option for Alzheimer's disease through multiple functions and pathways.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033945:  The endocannabinoid system has been shown to be associated with neurodegenerative diseases and dementia. We review the preclinical and clinical data on cannabinoids and four neurodegenerative diseases: Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD) and vascular dementia (VD). Numerous studies have demonstrated an involvement of the cannabinoid system in neurotransmission, neuropathology and neurobiology of dementias. In addition, several candidate compounds have demonstrated efficacy in vitro. However, some of the substances produced inconclusive results in vivo. Therefore, only few trials have aimed to replicate the effects seen in animal studies in patients. Indeed, the literature on cannabinoid administration in patients is scarce. While preclinical findings suggest causal treatment strategies involving cannabinoids, clinical trials have only assessed the suitability of cannabinoid receptor agonists, antagonists and cannabidiol for the symptomatic treatment of dementia. Further research is needed, including in vivo models of dementia and human studies.  The transition of findings from bench to bedside and the extension of results from small clinical trials should be on the research agenda for the near future. Because treatment strategies for dementia are so preliminary at the current state of knowledge and the need for a cure is so desperate, it is worth pursuing the quest for one or more cannabinoid compounds in the field.


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1253627:   The goal of the present study was to test the hypothesis that the potent synthetic cannabinoid HU210 is able to promote hippocampal neurogenesis, leading to the anxiolytic and antidepressant effects of cannabinoids. We demonstrate here that both HU210 and the endocannabinoid AEA promote proliferation of embryonic hippocampal NS/PCs without significant effects on their differentiation, resulting in more newborn neurons. The effects of HU210 on adult hippocampal neurogenesis were quantified in freely moving rats and were correlated with behavioral testing. We show that 1 month after chronic HU210 treatment, rats display increased newborn neurons in the hippocampal dentate gyrus and significantly reduced measures of anxiety- and depression-like behavior. Thus, cannabinoids appear to be the only illicit drug whose capacity to produce increased hippocampal newborn neurons is positively correlated with its anxiolytic- and antidepressant-like effects.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481530On the basis of biological effects of cannabinoids, it was suggested that in old individuals cannabinoid receptor ligands may have even beneficial effects against age-related cognitive deficits [239]. Only a low number of publications exists focusing on the influence of cannabinoids on brain functions in healthy aged animals, but their results support this hypothesis: the CB1 receptor agonist WIN-55212-2 attenuated spatial memory impairment, reduced the number of activated microglia [240] and triggered neurogenesis [216] in aged rats. Similar to CB1 agonists, CB2 agonists or blockers of FAAH also enhanced proliferation of neuronal progenitor cells in old individuals [215]. These reports and the accelerated ageing phenotype of CB1 knockout animals together suggest that elevation of cannabinoid system activity ameliorates symptoms of brain ageing.







Cannabis -vs- Alzheimer's

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