Research Summary:

One of the most common neurodegenerative diseases and one of the most financially burdensome to modern society, Alzheimer’s disease begins with symptoms of forgetfulness, disorientation, mood swings, and loss of motivation. It progresses to the loss of bodily functions and death typically occurs in 3 to 9 years after diagnosis. Despite huge expenditures, no treatment to slow progress has been found although some do temporarily improve symptoms. In the brain, the disease is characterized by the buildup of beta-amyloid plaques (Aβ) and neurofibrillary tangles, the overactivation of glial cells (the immune cells of the brain) and loss of neuronal connections. The cause is unknown except for the ~2% of cases that arise from a dominant gene for early-onset familial Alzheimer’s disease.

A diverse body of research suggests using the phytocannabinoids or drugs that target the endocannabinoid system as a treatment for both the symptoms and disease progression of Alzheimer’s. In humans:

In preclinical research, CBD helped the microglial cells to better destroy amyloid-β plaques, it protect the brain via its antioxidation ability and prevented disease progression via the scavenging of reactive oxygen species. In mice, CBD helped to maintain their spatial memory, reduce their anxiety and lessen fear-associated freezing as well as rescuing memory impairment. CBD also improved cognition and decreased anxiety as well as enhancing the immune system response and the pathway for autophagy (regulated cell recycling and digestion of damaged or unnecessary cellular components). In a mouse model of familial Alzheimer’s disease, CBD lessened symptoms, slowed cognitive decline and even modulated the expressions of genes related to Alzheimer’s. In mice, THC slowed memory decline and chronic use reduced their plaques and restored memory function. Low doses of THC decreased biomarkers of the disease and in computer simulations, THC destabilized the Aβ plaques. In a tissue model of Alzheimer’s disease, CBD lowered the aggregation of the tau proteins and 9 of the non-psychoactive cannabinoids helped to protect the neurons, lower inflammation, reduce oxidative damage and increase balance to the proteins and mitochondria (powerhouse of the cell).

The endocannabinoid system is a robust target for treating Alzheimer’s disease. In rats, activation of the CB1 receptor lessened cognitive impairment by lowering oxidative stress and enhancing neurogenesis (the creation of new brain cells). In mice, inhibiting the FAAH enzyme (which breaks down anandamide) lowered inflammation of the microglia via several different processes and in rats with dementia, protected the brain and preserved spatial learning and memory. In mice, a drug that blocks both FAAH and MAGL (the enzyme that breaks down 2-AG) lowered neuroinflammation, oxidative stress and levels of amyloid β plaques. Genetically, problems in endocannabinoid retrograde transmission seem to be a predictor of the disease. Most of all, the CB2 receptor is a key (and well-studied) target:

Other cannabinoids and related molecules have been shown to help. PEA seems to help via the astrocytes of the brain and in a tissue model of Alzheimer’s disease, PEA and luteolin (a flavonoid commonly paired with PEA) reduced neuronal inflammation. In a different cellular model, PEA protected the neurons and increased their survival. Some cannabis terpenes provided neuroprotection against the toxic neurofibrillary tangles. The diabetes drug metformin may help with neurogenesis and spatial memory via its regulation of MAGL. 

From the Project CBD Archives:

THC & CBD for Dementia

A pilot study demonstrates that cannabis extracts can be safely used for symptoms of severe dementia.

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