Many parallels exist between cannabis and psychedelics. Among them are the diverse therapeutic effects for which both classes of drugs are now being investigated, from fighting pain and inflammation to aiding treatment of some psychiatric disorders. Also on the list: Alzheimer\u2019s Disease, the most common neurodegenerative disease with as many as 6.2 million Americans living with the condition. (The next most prevalent is Parkinson\u2019s Disease at 1.2 million.)<\/p>\n
Cannabinoids may be good candidates for treating Alzheimer\u2019s Disease.<\/p>\n
On the psychedelic front, a review article published last year in the journal Frontiers in Synaptic Neuroscience1\u00a0makes a strong case for LSD<\/span> and psilocybin as potential treatments for this progressively disabling condition. A study now underway at Johns Hopkins University\u2019s Center for Psychedelic and Consciousness Research and another published in 20192\u00a0by psychedelic medicine company Eleusis signal serious interest in Alzheimer\u2019s among the field\u2019s heavy hitters.<\/p>\n And in the world of cannabis science, the plant has been studied as a potential treatment for Alzheimer\u2019s Disease since at least the turn of the century. Today interest in the subject is higher than ever. The scientific publisher Frontiers recently issued a call for papers on \u201ctargeting the endocannabinoidiome in neurodegenerative disorders,\u201d recognizing the subject as a \u201chot research area.\u201d (The term \u201cendocannabinoidome\u201d refers to the expanded endocannabinoid system, including additional mediators, enzymes, and molecular targets.)<\/p>\n In September 2021 alone, three papers appeared in the scientific literature summarizing much of what\u2019s known about Alzheimer\u2019s Disease and the endocannabinoid system.<\/p>\n An article published in the journal Brain Sciences3\u00a0reviews how the endocannabinoid system (ECS<\/span>) may be involved in the development of Alzheimer\u2019s Disease \u2013 and how cannabidiol (CBD<\/span>) and other cannabinoids may be used to help treat it. The discussion gets quite technical, but here are the authors\u2019 highlights of what the science from the last couple decades suggests:<\/p>\n Postmortem analysis has revealed changes to several components of the ECS<\/span> in the brains of Alzheimer\u2019s patients. Expression of CB1<\/span> cannabinoid receptors is decreased, while expression of CB2<\/span> receptors is markedly increased in the frontal or parahippocampal cortex, \u201cprobably in a time-dependent manner.\u201d While both THC<\/span> and CBD<\/span> offer promise in this respect and are known to be neuroprotective, \u201cthe concomitant psychotropic effects of THC<\/span> pose a problem,\u201d the authors write. (THC<\/span>\u2019s intoxicating effects are mediated by CB1<\/span>, though the compound also binds to CB2<\/span>; CBD<\/span> does not have a strong affinity for either.) As a result, CBD<\/span> has attracted increasing attention for its therapeutic potential.<\/p>\n A second recent review, published in the Journal of Neuroscience Research4\u00a0in early September, takes a slightly different tack. Instead of focusing on plant cannabinoids, it draws upon many of the same factors linking the ECS<\/span> with Alzheimer\u2019s Disease to make a case for selectively targeting CB2<\/span> (which does not mediate psychotropic effects) when developing novel drugs to treat Alzheimer\u2019s and related conditions.<\/p>\n \u201cIn the treatment of neurodegenerative diseases, CB2<\/span> agonists have shown promising results,\u201d the India-based authors write. (An \u201cagonist\u201d activates a receptor and causes it to signal, whereas an antagonist blocks the receptor.) \u201cThe experimental evidence suggests that they may be useful in the management of Alzheimer\u2019s Disease by reducing inflammation, tau hyperphosphorylation, beta-amyloid aggregation, [and] oxidative stress, and improving cognitive function.\u201d<\/p>\n The paper cites numerous examples of selective CB2<\/span> agonists developed and tested for treating pain, arthritis, inflammation, and other conditions by companies including GlaxoSmithKline, Glenmark Pharmaceuticals, Corbus Pharmaceuticals, and Eli Lilly. Thus far, however, medical scientists have not been able to translate early-phase clinical trials involving CB2<\/span> agonists into viable, clinically effective pharmaceuticals.<\/p>\n In recent years the gut microbiome has emerged as a fascinating player in human health and disease. Disturbances to this system have been associated with a broad range of adverse outcomes including obesity, cancer, and (you guessed it) neurodegenerative disorders such as Alzheimer\u2019s and Parkinson\u2019s.<\/p>\n Less often addressed in popular accounts of the gut microbiome are its interactions with the endocannabinoid system. As Project CBD<\/span> explained in a 2020 article, the ECS<\/span> serves as a sort of bridge between resident bacteria and the body itself, including the brain, by relaying signals back and forth within this symbiotic, mutually beneficial relationship.<\/p>\n In a recent review in the journal Life5 , a team of Italian researchers uses this same metaphor to conceptualize how the ECS<\/span> may be key to mediating the connection between gut flora dysbiosis and Alzheimer\u2019s physiopathology. The two interacting systems may serve as \u201ccommon denominators\u201d in the disease, the researchers suggest. \u201cThe overlapping roles of the encodcannabinoid system and the microbiome\u2026suggest that a novel approach such as modulating the microbiota via [the ECS<\/span>] may provide new therapeutic perspectives for treating AD<\/span>,\u201d they conclude.<\/p>\n \u200bNate Seltenrich, an independent science journalist based in the San Francisco Bay Area, covers a wide range of subjects including environmental health, neuroscience, and pharmacology.<\/p>\n Copyright, Project CBD<\/span>. May not be reprinted without permission.<\/p>\n \u00a0<\/p>\n<\/div>\nCBD<\/span> for Alzheimer\u2019s Disease<\/h2>\n
\nIncreased expression of CB2<\/span> receptors is pronounced in and around amyloid plaques (aggregates of abnormally configured proteins that are considered a hallmark of Alzheimer\u2019s Disease and cognitive decline), indicating a correlation between the ECS<\/span> and plaque deposition.
\nExpression of the enzymes FAAH<\/span> [fatty acid amide hydrolase] and MAGL<\/span> [monoacylglycerol lipase] \u2013 which metabolize the endocannabinoids anandamide and 2-Arachidonoylglycerol (2-AG<\/span>) , respectively \u2013 increases in the brains of Alzheimer\u2019s patients. So too does expression of a third key enzyme, DAGL<\/span> [diacylglycerol lipase], which synthesizes 2-AG<\/span>.
\nGiven the modulatory effects of cannabinoids on the ECS<\/span>, cannabinoids may be good candidates for treating Alzheimer\u2019s Disease. Clinical trials have already reported that cannabinoids might be useful for reducing some symptoms in patients with Alzheimer\u2019s or dementia.<\/p>\nTargeting Cannabinoid Receptor 2 to Treat Dementia<\/h2>\n
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<\/div>\nAlzheimer\u2019s &<\/span> Gut Microbiota<\/h2>\n
Footnotes<\/h2>\n
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