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The Caffeine Molecule May Harm Your Endocannabinoid System

Dragana Komnenov PhD
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Is it possible that coffee is harming us?

When I think of sipping on a nice brew, it normally brings to mind things like: a little morning pick-me-up, socializing with friends, or taking a break in the workday. Never have I considered that the caffeine molecule could throw my entire endocannbinoid system out of whack!

And did you know that besides the caffeine molecule, coffee also contains hundreds of other questionable compounds? All of these can interfere with aspects of disease development and/or prevention. The same is true for tea, energy drinks and soft drinks rich in caffeine.

A Coffee Trial Exposes Risks to Health

A study out of Finland looked at the changes to body metabolites with controlled coffee intake. This three-stage clinical trial lasted three months and featured habitual coffee drinkers younger than 65.

During the first month, the participants abstained from all coffee drinking. In the second month, they consumed 4 cups per day (1 cup = 150ml). This amount then doubled during the third month to 8 cups of coffee daily.

A total of 47 participants completed the trial. Fasting blood samples were collected from the participants after each of the three coffee stages and serum samples were analyzed for various metabolites.

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Unsurprisingly, over 100 body metabolites change with increases in coffee consumption. Some dramatically decrease, especially after an 8 cups per day amount. Arachidonate, a precursor to anandamide (AEA) and 2-arachydonylglycerol (2-AG) significantly decreases with increased coffee intake. Other ethanolamines, which structurally resemble and share biosynthetic and degradation pathways with AEA and 2-AG also decrease.

This initial study highlighted some of the damaging effects of heavy coffee drinking to endocannabinoid tone. The results raise the possibility that chronically elevated coffee consumption could wreak havoc on systems regulated by endocannabinoids. These include the immune system, sleep cycles, appetite control and cognitive functioning.

Rodent Study Finds Caffeine Molecule May Protect Against Stress Damage

These findings may have particularly high impact in individuals undergoing stressful life events, since caffeine consumption typically increases under stress. Likewise, increased coffee consumption is correlated with increases in stress-induced neurotransmitter changes, cortisol levels and depressive symptoms. Stress downregulates CB1 receptor-mediated transmission, suggesting the existence of the interplay between stress, caffeine consumption and cannabinoids signaling.

A study in mice looked at these associations.  Researchers wanted to address the sensitivity of CB1 receptors in the brain after the mice received caffeine in their drinking water. A second part of the study investigated how synaptic transmissions change because of stress. All of this takes place in the striatum area of the brain. It plays a key role in the central effects of caffeine and is richly endowed in cannabinoid receptors.

The mice received a dose of caffeine equivalent to drinking 3-5 cups of coffee a day. The synaptic responses to CB1 receptor activation remained unaltered for the first 20 days of the experiment.  These were, however, markedly more sensitive after 30 and 45 days.

CB1 receptors experienced down-regulation in animals exposed to chronic stress. But, even acute administration of caffeine for just one day was able to rescue synaptic sensitivity to CB1 receptor activation in the striatum. This suggests that caffeine intake during stressful times has beneficial effects. It appears to protect CB1 receptor function against the psycho-emotional consequences of stress.

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Should We Cut Back on Coffee Consumption?

Future studies need to determine whether the changes to endocannabinoid tone and CB1 receptor function are different after chronic vs. acute caffeine molecule consumption. This data certainly suggest a diminishing effect on endocannabinoid tone and CB1 receptor abundance after extended periods of heavy coffee drinking.

Consuming cannabis to offset damage of the caffeine molecule seems to be beneficial. This could be particularly applicable during extended periods of stress where individuals consume increased caffeine doses in order to preserve central and peripheral systems that are under the control of cannabinoid signaling.

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Dragana Komnenov
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