Caffeine reduces brain blood flow. So how does it energize our minds?

While more controlled psychostimulants like amphetamines and cocaine facilitate a rush of blood to the whole brain, caffeine actually restricts blood flow overall. 

Caffeine-induced resting brain entropy increase in a large portion of the cerebral cortex. (Scientific Reports ISSN 2045-2322)
Caffeine-induced resting brain entropy increase in a large portion of the cerebral cortex. (Scientific Reports ISSN 2045-2322)

Caffeine is the world's most popular psychostimulant. In the United States, more than 90 percent of adults regularly consume caffeine and the average 'user' takes in about 300 milligrams per day, the equivalent of 3 cups of coffee. 


Beverages infused with caffeine are by far the most common way the chemical is administered. As a mild stimulant, caffeine is prized for its effects on cognition, attention and alertness. Drinking coffee, tea or soda is an essential and acceptable part of the day for many adults while other psychostimulants—like amphetamines and cocaine—remain highly controlled. 

One difference between illicit stimulants and coffee is the effect they have on the brain. While more controlled psychostimulants facilitate a rush of blood to the whole brain, caffeine actually restricts blood flow overall. 

A new study published in Nature's Scientific Reports looks at this counterintuitive fact and explains caffeine's beneficial effect by way of 'resting brain entropy', or BEN. Despite decreasing blood flow to the brain, caffeine leaves individual regions more stimulated. The stimulating effects are uneven, however, creating a chaotic balance of energy when the stimulant is in full force. The greater unevenness in stimulation throughout the brain, the higher the entropy.

Caffeine consumption decreases cerebral blood flow

Caffeine induced whole brain cerebral blood flow (CBF) decrease. Paired-t test showed that compared with control condition (no caffeine), caffeine induced whole brain CBF decrease. (a) is the thresholded t map presented in 2D, blue means lower after caffeine ingestion, p < 0.001. (b) is the same result presentation in 3D. (Scientific Reports ISSN 2045-2322)


According to researchers, "caffeine caused BEN increase in a big portion of the cerebral cortex with the highest increase in lateral prefrontal cortex, the DMN, visual cortex, and motor network." 

"Caffeine-induced BEN increase varied across the brain with relatively larger BEN increase in prefrontal cortex, lateral striatum, visual cortex, and motor area. This distribution may be a result of caffeine effects on cognition: caffeine has the strongest impact on attention, vigilance, and action/motion function which are mainly subserved by the aforementioned brain regions."


Caffeine consumption increases resting brain entropy 

Caffeine induced BEN increase in a large portion of the cerebral cortex. Paired-t test showed that compared with control condition (no caffeine), Caffeine induced BEN increase in a large portion of the cerebral cortex with the highest increase in lateral prefrontal cortex, the DMN, visual cortex, and motor network. (a) is the thresholded t map presented in 2D, blue means lower after caffeine ingestion, red means higher after caffeine ingestion, p < 0.001, AlphaSim corrected (cluster size threshold is 270). (b) is the same result presentation in 3D. (Scientific Reports ISSN 2045-2322)

 

Because stimulation to brain regions is not vascular—overall blood flow to the brain decreases after caffeine is consumed—researchers conclude that caffeine's stimulating effects are a result of greater neuronal activity. And despite what advocates for moderation have claimed for decades, there appear to be no negative side effects to caffeine consumption above average amounts. 

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Credit: NASA
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CRISPR therapy cures first genetic disorder inside the body

It marks a breakthrough in using gene editing to treat diseases.

Credit: National Cancer Institute via Unsplash
Technology & Innovation

This article was originally published by our sister site, Freethink.

For the first time, researchers appear to have effectively treated a genetic disorder by directly injecting a CRISPR therapy into patients' bloodstreams — overcoming one of the biggest hurdles to curing diseases with the gene editing technology.

The therapy appears to be astonishingly effective, editing nearly every cell in the liver to stop a disease-causing mutation.

The challenge: CRISPR gives us the ability to correct genetic mutations, and given that such mutations are responsible for more than 6,000 human diseases, the tech has the potential to dramatically improve human health.

One way to use CRISPR to treat diseases is to remove affected cells from a patient, edit out the mutation in the lab, and place the cells back in the body to replicate — that's how one team functionally cured people with the blood disorder sickle cell anemia, editing and then infusing bone marrow cells.

Bone marrow is a special case, though, and many mutations cause disease in organs that are harder to fix.

Another option is to insert the CRISPR system itself into the body so that it can make edits directly in the affected organs (that's only been attempted once, in an ongoing study in which people had a CRISPR therapy injected into their eyes to treat a rare vision disorder).

Injecting a CRISPR therapy right into the bloodstream has been a problem, though, because the therapy has to find the right cells to edit. An inherited mutation will be in the DNA of every cell of your body, but if it only causes disease in the liver, you don't want your therapy being used up in the pancreas or kidneys.

A new CRISPR therapy: Now, researchers from Intellia Therapeutics and Regeneron Pharmaceuticals have demonstrated for the first time that a CRISPR therapy delivered into the bloodstream can travel to desired tissues to make edits.

We can overcome one of the biggest challenges with applying CRISPR clinically.

—JENNIFER DOUDNA

"This is a major milestone for patients," Jennifer Doudna, co-developer of CRISPR, who wasn't involved in the trial, told NPR.

"While these are early data, they show us that we can overcome one of the biggest challenges with applying CRISPR clinically so far, which is being able to deliver it systemically and get it to the right place," she continued.

What they did: During a phase 1 clinical trial, Intellia researchers injected a CRISPR therapy dubbed NTLA-2001 into the bloodstreams of six people with a rare, potentially fatal genetic disorder called transthyretin amyloidosis.

The livers of people with transthyretin amyloidosis produce a destructive protein, and the CRISPR therapy was designed to target the gene that makes the protein and halt its production. After just one injection of NTLA-2001, the three patients given a higher dose saw their levels of the protein drop by 80% to 96%.

A better option: The CRISPR therapy produced only mild adverse effects and did lower the protein levels, but we don't know yet if the effect will be permanent. It'll also be a few months before we know if the therapy can alleviate the symptoms of transthyretin amyloidosis.

This is a wonderful day for the future of gene-editing as a medicine.

—FYODOR URNOV

If everything goes as hoped, though, NTLA-2001 could one day offer a better treatment option for transthyretin amyloidosis than a currently approved medication, patisiran, which only reduces toxic protein levels by 81% and must be injected regularly.

Looking ahead: Even more exciting than NTLA-2001's potential impact on transthyretin amyloidosis, though, is the knowledge that we may be able to use CRISPR injections to treat other genetic disorders that are difficult to target directly, such as heart or brain diseases.

"This is a wonderful day for the future of gene-editing as a medicine," Fyodor Urnov, a UC Berkeley professor of genetics, who wasn't involved in the trial, told NPR. "We as a species are watching this remarkable new show called: our gene-edited future."

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