In preclinical studies, a therapeutic dose of THC breaks down amyloid plaques and restores neuronal loss associated with Alzheimer’s.
Neurodegenerative diseases like Alzheimer’s compromise neuronal tissue health and they usually involve accumulation of defective proteins. These take the form of “plaques.”
These plaques are a hallmark of Alzheimer’s disease (AD). The depositing of amyloid plaques (called Aß plaques), results in the accumulation of folded proteins called “amyloid beta.”
The Therapeutic Potential of Cannabinoids in Alzheimer’s
Other components of this syndrome include the formation of neurofibrillary tangles containing tau protein as well as selective neuronal loss and cognitive deficits. The knowledge of the therapeutic potential of cannabinoids in neurodegenerative diseases is on the rise. It’s rising both as a symptom relief strategy, and as a treatment for the neuronal loss.
Cannabinoid signaling may regulate AD pathology. This comes from post-mortem examinations of human AD patients. These show increased CB1 and CB2 receptors on microglia. Microglia is a cell type in the brain that regulates inflammatory response. The study finds lower CB1 expressions in non-plaque areas.
These changes in the endogenous cannabinoid system have at least two-fold significance. First off that the endocannabinoid system regulates AD progression. Secondly, and more importantly, these findings suggest that exogenous cannabinoids (like THC and CBD) could have therapeutic benefits in AD pathophysiology. If administered in order to restore the cannabinoid balance.
THC Preserves Neurons
Subsequent pre-clinical studies have shown that administration of THC at 3mg/kg per day for four weeks lead to a reduction in Aß plaques and preservation of neurons. Additionally, according to research in human dementia patients, administration of synthetic THC analog, dronabinol (2.5mg) daily for two weeks improved neuropsychiatric profiles for agitation and aberrant motor and night time behaviours.
One research group has recently shown in a study — published in the Journal of Alzheimer’s Disease (2014) — that THC has anti- Aß properties in vitro. Namely, they discovered that incubating cells producing Aß with THC results in an arrest of Aß production. The authors also underlined that the amount of THC they used to treat the cells corresponds to extremely low doses. These doses are a thousand times lower than the doses of THC that cause cognitive impairments in rat studies. Lastly, they found no cytotoxic (toxic to living cells) side effects of this dose of THC in cells so this suggests that this treatment would be safe and effective in pre-clinical studies based on this data.
How is THC as a Treatment for Alzheimer’s Possible?
One research group has taken the cannabinoid research into Alzheimer’s to another level in their attempt to pinpoint exactly how THC breaks down Aß production at the molecular level. In the study — published by the American Chemical Society (2006) — the research group performed both computational and experimental analyses. As they attempted to predict the fit between the THC molecule and one particular enzyme. The name of this enzyme is acetylcholinesterase and it’s responsible for breakdown of the neurotransmitter acetylcholine. Down regulation of acetylcholine by acetylcholinesterase is one of the most dramatic neurotransmitter perturbations observed in AD. And in fact, the four FDA-approved drugs have a specific design to target this cholinergic system.
The researchers found that indeed, THC with its particular chemical structure fits into the acetylcholinesterase enzyme active site, which is the part of the protein that is responsible for exerting the actual enzymatic action (i.e. deactivation of acetylcholine). The functional experiments that they performed confirmed that this inhibition of acetylcholinesterase by THC led to reduction of Aß aggregation. Additionally, according to this 2012 study — published in multiple journals — THC is a considerably more potent inhibitor of acetylcholinesterase-induced Aß deposition compared to the approved drugs for Alzheimer’s. Drugs like donepezil and tacrine, which according to research only reduce Aß deposition by only twenty two percent and seven percent, respectively.
The Future of THC as a Treatment for Alzheimer’s
The data demonstrates a clear implication of THC in reducing Aß plaque formation in Alzheimer’s disease. This is one of the hallmarks of this disease’s pathology, too. The finding that THC acts as an inhibitor of acetylcholinesterase, proves the therapeutic benefits of THC in treating Alzheimer’s. Scientifically speaking, this is crucial in the development of new therapies, and the initiation of clinical trials.