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THC May Help Regulate Circadian Rhythm And Aging

Dragana Komnenov PhD
Aging Woman

Cannabinoids may help keep that circadian clock functioning at peak levels.

Environmental cues, such as light and temperature, are factors that affect an organisms’ behavior. It helps them align feeding, sleep, and other activities according to the time of day. Species use these cues to improve of survival and fitness over time. Collectively, the phenomenon is called circadian rhythm or circadian clock. It dictates some of the most basic needs of an individual.

Although the observation that animals’ behavior is tailored to the time of day was made long ago, only relatively recently have the biological and physiological mechanisms that explain these processes started to be studied. These studies revealed the existence of circadian clock genes, and even more importantly that the changes in the clock genes occur during aging.

Circadian Rhythm and Aging

One of the most reported symptoms of disrupted circadian rhythm in aging is disturbed sleep. Sleep quality and consistency are two of the most affected aspects of circadian biology that decline as we age. Furthermore, because sleep is an integral factor in consolidation of memory, sleep disruptions in aging are often happening at the same time with cognitive and/or neurodegenerative diseases. Body temperature oscillations (i.e. higher during the daytime and lower during the nighttime) and the production of a human growth hormone are additional physiological factors that are negatively impacted by a dysregulated circadian rhythm that comes with aging.

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The Endocannabinoid System Changes as we Age

Numerous studies demonstrate that the endocannabinoid system regulates sleep, hunger, body temperature and cognitive function. Advancing age will cause disruption and dysfunction in circadian rhythm.

Not surprisingly, the endocannabinoid system itself is modulated as we age. More recent studies, done in humans using PET scans, show sex-specific increases in CB1 receptor reactivity in aged females. Changes occur not only at the level of the receptors, but also the endocannabinoids. For example, 2-AG decreases in advanced age.

Likewise, studies in aging mice showed that CB1 deficiency leads to age-related behavioral disturbances much earlier than mice that have the CB1 gene intact. These results indicate that the preservation of endocannabinoid tone is important for proper cognitive function during aging.

Furthermore, recent data in primates indicate that the endocannabinoid system components themselves are under the regulation of circadian rhythm. Namely, the making of new CB1 receptors is under circadian modulation. This would indicate that the available cannabinoid receptor abundance varies across the daytime and nighttime.

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Can Cannabinoids Treat These Age-Related Changes?

A significant body of evidence suggests that low doses of THC (≤ 3mg/kg in rodents) and other cannabinoids may be therapeutic for certain aspects of age-related pathophysiologies. On the other hand, high doses (≥ 3mg/kg in rodents and ≥ 0.15mg/kg in humans, the responses to THC can be deleterious.

Furthermore, the time of day of THC administration can drastically affect the physiological responses, which may tie back to the finding that cannabinoid receptor expression is under circadian modulation. 

The implications of these findings are far reaching. Prescribing physicians must consider, not only dosing, but age and time of day taking cannabis.

In any event, cannabinoids pharmacology shows great promise in treating some of the age-related declining aspects of physiology, although we have more to learn about the circadian modulation of the endocannabinoid genes and the optimal window for treatments.

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Dragana Komnenov
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