Saturday, 11 July 2015

Here's how different drugs change your brain.

We know different drugs make us experience the world around us in very different ways.
But what exactly are these drugs doing to the brain to prompt these feelings?
Here's a look into four types of drugs and their effect on the brain as shown in snapshots of fMRI scans or infographics.
It's important to keep in mind that some of the images look at the brains of chronic users,
while others look at the brains of people who have used only a few times or at the brains of lab animals. Brain scans are also captured in the laboratory, which can't exactly mirror real life scenarios. The snapshots below are only a clue into how these substances affect our brains as a whole.

Magic mushrooms

Recent research suggests that tripping on magic mushrooms may change the mind by quieting traditional brain activity and jump-starting new connections between areas of the brain that previously didn't communicate with one another. Shrooms' key psychoactive ingredient, and the one responsible for these changes, is psilocybin.
Say you were to represent the brain as a circle, with various sections of the brain as smaller colorful circles along the bigger circle's edges. You could then show the brain's activity (the sending and receiving of various messages from one region of the brain to another) as thin bands of blended color across the circle.
A non-drugged brain would look like the illustration on the left. But a brain on psilocybin, as shown in the illustration on the right, would look quite different. The regional circles along the edges would be darker to represent the uptick in activity inside each of them. Similarly, the multicolored lines across the brain would multiply and get thicker.

These new connections may be the "magic" ingredient causing users to experience things like seeing sounds or hearing colors, suggest the study authors. They could also be responsible for giving magic mushrooms some of their antidepressant qualities, since they quiet activity in the part of the brain responsible for the sense of self, or ego.
And while these sparks of activity may seem erratic, the research suggests things aren't quite that simple.
"The brain does not simply become a random system after psilocybin injection," the researchers wrote, "but instead retains some organizational features, albeit different from the normal state."
In other words, if the information in your brain was shared across an interconnected and heavily-trafficked system of highways, psilocybin doesn't simply take different ways through them — it builds new ones.
As with any drug, psilocybin doesn't come without health risks. People who use shrooms may experience unpleasant hallucinations, for example.
More research on psychedelic drugs like magic mushrooms is needed. Only recently has the US government begun to loosen its restrictions on studying the medical uses of psychedelics. Many scientists have argued these legal issues have made conclusive research on psychoactive drugs "difficult and in many cases almost impossible."

Marijuana

If you were to peek inside the brain of someone who regularly smoked marijuana, you'd find several notable differences between it and the brain of a nonsmoker.
First, you'd see that the orbitofrontal cortex, a critical part of the brain that helps us process emotions and make decisions looked smaller, as if it had shrunk. But if you were to look at that section more closely, you'd also see that the connections passing through it were also stronger and thicker.
In a recent study, scientists used a combination of MRI-based brain scans to get one of the first comprehensive, three-dimensional pictures of the brains of adults who have smoked weed at least four times a week, often multiple times a day, for years.
Here's an image from the study. In it, you can see extra activity in the shrunken orbitofrontal cortices of regular smokers (bottom row) that isn't present in the brains of nonsmokers with a normal-sized orbitofrontal cortex (top row). All that extra action corresponds with stronger cross-brain connections there.

If heavily using marijuana is causing the orbitofrontal cortex to shrink, smokers could be developing thicker cross-brain connections as a means of compensating, the scientists write in their paper.
But they can't say for sure that that's the case.
Why? Because the relationship could go the other direction (meaning having a naturally smaller orbitofrontal cortex could make someone more likely to smoke a lot of pot), or something else could be causing both the things the researchers observed (the shrunken brain region and the behavior of smoking).
One recent study, for example, found that children as young as 12 who had smaller orbitofrontal cortices were significantly more likely to start smoking weed by the time they were 16 — a hint that the brain differences came first.

Alcohol

You know drinking can blur your vision, slur your speech, mess with your memory, and make you slower to react. But if you tend to binge when you drink — meaning you typically down four or more drinks (if you're a woman) or five or more drinks (if you're a man) in two hours — it could also be affecting the way your brain processes information in the long term.
In a recent study, scientists had two groups of people — binge drinkers and people who drank regularly but never binged — take a test of their working memory while they looked at their brains under an fMRI scanner. First, the participants had to press a button when a certain number was displayed. Then, they had to press a button when the number that was shown was the same number that had been shown two numbers before.
While both groups performed the same, the binge drinkers showed significantly more activity across their brains than the non-bingers, especially in regions of the brain that the non-bingers didn't use. The more drinks they took, the more abnormal brain activity they showed when completing the task.
Here's an image from the study. Activity in binge-drinkers is shown in red; activity in non-binge-drinkers is shown in green. Areas where activity took place in both groups is shown in dark grey.

Why would binge drinkers and non-binge drinkers use different parts of their brains for the same task?
For the same reason, the researchers supposed, that you'd recruit a group of friends to help you move a desk that you couldn't lift simply on your own. Since the traditional brain regions can no longer accomplish the task alone, new areas are being recruited to take on part of the workload.
Again, researchers can't yet say that there's a causal relationship between drinking and this kind of brain activity, but the finding squares with other research on alcohol and the brain.
In a 2014 study comparing people dependent on alcohol with those who weren't, the dependents took far more time to do the same task with the same level of accuracy. Yet they had heightened activity in different regions of the brain that the non-dependents weren't using to complete the task.
"Imagine the brain as an engine," says Massachusetts General Hospital Center for Addiction Medicine clinical researcher Jodi Gilman, who wasn't involved in the study mentioned above, but has published several similar studies on marijuana and alcohol use and the brain. "You have to rev it up more to get the same work done."

Cocaine

Whether it's snorted, smoked, or injected, cocaine enters the bloodstream and penetrates the brain in a matter of seconds. Once there, it causes an intense feeling of euphoria — its characteristic "high" — by overwhelming the mind with the feel-good chemical dopamine. The sensation of pleasure is so powerful that some lab animals, when given a choice, will choose cocaine over food until they starve to death.
The part of the brain cocaine affects the most includes key memory centers that help us recall where the source of pleasure came from. When we experience a cocaine high, these brain areas form memories of our pleasurable experience and the places or people that were involved in our experience of getting the drug. This is why going back to the original spot where you've used cocaine — or simply seeing pictures of someone else using — can trigger a desire to use.
In mice who've been dosed with cocaine, repeated exposure to the drug unleashes a host of changes in the brain cells in the prefrontal cortex (a region that helps with decision making and inhibition). The more they get the drug, the more likely they are to access it again when given the option. These changes are likely part of what hooks regular human users too.
But what about people who've only tried the drug once? Bad news, experimenters: Scientists have recently found evidence that the drug may start to affect the brain's structure after just a single dose.
Here's a set of time-lapse images showing how the wiring of a live mouse's brain changes over a few days (A = day 1, B = day 2, etc.) of cocaine use. Mice with more spines were also more likely to use cocaine repeatedly, even if it meant leaving an environment they preferred. Green arrows show where new spines have grown, blue arrows show where spines have decayed, and yellow arrows show where spines have remained stable.

For the study that image is from, researchers gave mice the option of picking a vanilla or cinnamon-scented chamber (a door between the chambers was left open so they could pick the one they liked best). The next day, they were given cocaine and placed in the chamber that was not their preferred side with the door between the chambers closed. On the third day, they were placed in the chambers again but with the door open.
Almost all of the mice picked the chamber where they'd been given the cocaine instead of the one whose smell they liked better.
When they looked at the brains of the mice under a microscope, they found a possible reason: Just two hours after they'd been dosed with cocaine, new connections had sprouted between brain cells in the frontal cortex. Mice with more new connections were also more likely to have chosen the chamber where they'd gotten the cocaine over the chamber whose smell they'd preferred.
While mice don't have the same complex brain structure humans do, their brains still have enough in common with ours to make them a useful model. The study's findings also appear to square with some existing studies of people addicted to cocaine.

Ecstasy

Decades of research suggest that the brains of chronic ecstasy users — people who pop a couple pills every weekend for years, or those who indulge in 10-20 pills in a weekend — have been fundamentally altered in a disturbing way.
Several key regions which are vibrantly active in non-users appear far quieter, as if dulled.
2013 study, for example, found that activity (measured using PET scans of glucose metabolism, a popular way to gauge action in the brain) in two key areas was much lower in the brains of frequent ecstasy users than it was in the brains of people who rarely or never used.
Since those regions are actively involved in learning and memory, the researchers also used a standard memory quiz to see how these chronic users fared at recalling information compared with the people who didn't use the drug. After playing an audio recording of 15 unrelated words, the scientists asked people in both groups to recall as many words as they could.
Not surprisingly, the chronic users performed far worse on the test compared with the non-users. 
More importantly, however, their scores on the quiz lined up surprisingly well with the brain changes the researchers observed. And the more they used over their lifetimes, the more intense the changes and the worse they performed on the test.
Here's a schematic from the study used to illustrate the changes the researchers observed in their participants' brains. Red areas show the regions with decreased activity, purple areas show decreased activity in people who used the most over their lifetimes, and green areas show decreased activity in people who performed poorly on the test

The perfect test would assess the same people before and after years of use to account for individual variability and other confounding factors, but such studies are nearly impossible in drug users.
And these findings square with other research, including a 2006 study of former chronic ecstasy users who had since stopped taking the drug. Even though they weren't currently taking the drug and hadn't used recently, these former users had similar difficulties with learning and memory.

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