Alzheimer’s disease and the endocannabinoid system

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There are many parallels between cannabis and psychedelics. Among them are the various therapeutic effects for which both classes of drugs are being investigated, from combating pain and inflammation to helping to treat some psychiatric disorders. Also on the list: Alzheimer’s disease, the the most common neurodegenerative disease with up to 6.2 million Americans living with this disease. (The next most common is Parkinson’s disease with 1.2 million).

On the psychedelic front, a review article published last year in the journal Frontiers in synaptic neuroscience1 makes a strong argument LSD and psilocybin as potential treatments for this progressively disabling disease. A study now let’s go at the Johns Hopkins University Psychedelic and Consciousness Research Center and another published in 20192 by the psychedelic medicine company Eleusis indicate a serious interest in Alzheimer’s among the great beaters of the field.

And in the world of cannabis science, the plant has been studied as a potential treatment for Alzheimer’s disease at least since the turn of the century. Today the interest in the subject is higher than ever. Scientific editor Frontiers recently published a call for papers on “targeting endocannabinoidism in neurodegenerative disorders,” recognizing the topic as a “hot research area”. (The term “endocannabinoidoma”Refers to the expanded endocannabinoid system, which includes additional mediators, enzymes, and molecular targets.)

In September 2021 alone, three articles appeared in the scientific literature that summarized much of what is known about Alzheimer’s disease and the endocannabinoid system.

CBD for Alzheimer’s disease

An article published in the journal Brain sciences3 reviews as the endocannabinoid system (ECS) may be involved in the development of Alzheimer’s disease and as cannabidiol (CBD) and other cannabinoids can be used to help treat it. The discussion becomes quite technical, but here are the highlights of the authors of what the science of the last two decades suggests:

  • Postmortem analysis has revealed changes in several components of the ECS in the brains of Alzheimer’s patients. Expression of CB1 cannabinoid receptors are reduced, while the expression of CB2 receptors increase markedly in the frontal or parahippocampal cortex, “probably in a time-dependent manner.”
  • Increased expression CB2 receptors is pronounced in and around amyloid plaques (abnormally configured protein aggregates that are considered a hallmark of Alzheimer’s disease and cognitive decline), indicating a correlation between ECS and plaque deposition.
  • Expression of enzymes FAAH [fatty acid amide hydrolase] i MAGL [monoacylglycerol lipase] – which metabolize the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), respectively – increases in the brains of patients with Alzheimer’s. So does the expression of a third key enzyme, DAGL [diacylglycerol lipase], which synthesizes 2-AG.
  • Given the modulatory effects of cannabinoids on the ECS, cannabinoids may be good candidates for treating Alzheimer’s disease. Clinical trials have already reported that cannabinoids may be helpful in reducing some symptoms in patients with Alzheimer’s or dementia.

While both THC i CBD offer a promise in this regard and are known to be neuroprotective, “the concomitant psychotropic effects of THC it’s a problem, “the authors write.THCThe intoxicating effects are mediated by CB1, although the compound also binds to CB2; CBD does not have a strong affinity for either.) As a result, CBD it has attracted increasing attention for its therapeutic potential.

Targeting the cannabinoid receptor 2 to treat dementia

A second recent review, published in the Journal of Neuroscience Research4 in early September, it takes on a slightly different look. Instead of focusing on plant cannabinoids, it relies on many of the same binding factors ECS with Alzheimer’s disease to argue for selective targeting CB2 (which does not mediate psychotropic effects) when new drugs are developed to treat Alzheimer’s and related conditions.

“In the treatment of neurodegenerative diseases, CB2 agonists have shown promising results, “write the authors based in India. (An” agonist “activates a receptor and causes it to signal, while an antagonist blocks the receptor.)” Experimental evidence suggests that they may be useful. in the treatment of Alzheimer’s disease by reducing inflammation, tau hyperphosphorylation, beta-amyloid aggregation, [and] oxidative stress and improved cognitive function “.

The paper cites numerous examples of selectivity CB2 Agonists developed and tested to treat pain, arthritis, inflammation and other conditions by companies such as GlaxoSmithKline, Glenmark Pharmaceuticals, Corbus Pharmaceuticals and Eli Lilly. So far, however, medical scientists have not been able to translate early-stage clinical trials involving CB2 agonists in viable and clinically effective pharmaceuticals.

Alzheimer’s & Intestinal microbiota

In recent years, the intestinal microbiome has become a fascinating player in human health and disease. Alterations in this system have been associated with a wide range of adverse outcomes, such as obesity, cancer, and (you guessed it) neurodegenerative disorders such as Alzheimer’s and Parkinson’s.

Its interactions with the endocannabinoid system are less frequently addressed in popular accounts of the intestinal microbiome. As a Project CBD explained in a 2020 article, el ECS it serves as a kind of bridge between resident bacteria and the body itself, including the brain, by relaying back and forth signals within this symbiotic and mutually beneficial relationship.

In a recent review in the magazine Life5 , a team of Italian researchers uses this same metaphor to conceptualize how the ECS may be key to mediating the connection between dysbiosis of the intestinal flora and the pathophysiology of Alzheimer’s. Researchers suggest that the two systems that interact may serve as “common denominators” of the disease. “The overlapping roles of the codcannabinoid system and the microbiome … suggest a new approach such as modulation of the microbiota using [the ECS] may offer new therapeutic perspectives for treatment AD”, They conclude.


Nate Seltenrich, a freelance science journalist based in the San Francisco Bay Area, covers a wide range of topics such as environmental health, neuroscience and pharmacology.

Copyright, Project CBD. Cannot reprint without permission.


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